Classification of acute myeloid leukemias

2002-05-01   Georges Flandrin 

1.Laboratoire d Hématologie, Hôpital Necker-Enfants Malades, Paris, France

Clinics and Pathology

Disease

First group WHO: AML with "recurrent cytogenetic translocations"

Note

Although the term "de novo" is not fully appropriate (see below "secondary AML"), this category of patients is usually referred as such in the literature since MDS or chemo/radiotherapy does not usually precede them either. The most commonly identified abnormalities are reciprocal translocations: t(8;21), inv(16) or t(16;16), t(15;17), t(11;17), t(9;11), t(6;9), t(1;22) and t(8;16). Molecular studies have shown that these structural chromosome rearrangements create a fusion gene encoding a chimeric protein. Most can be detected by RT-PCR including complex and cryptic cytogenetic variants. The altered expression and/or structure of cellular gene products leads to functional activation that may contribute to the initiation or progression of leukemogenesis.
The most frequent anomalies are : t(8;21)(q22;q22) - inv/del16( p13q22)/del(16)(q22)/t(16;16)(p13q22) - t(15;17)(q22;q21) - t(11;17)(q23;q21) - 11q23 , 
  • A first class of secondary AML include those patients with a longstanding exposure to environmental toxins, including smoking, occupational chemicals such as benzene and related petrochemicals. The importance of detailed occupational history of all patients cannot be overstated. , 
  • The second category corresponds to patients who received prolonged administration of chemotherapy and/or radiotherapy for non-MDS/MPS malignancies (epithelial cancer, malignant lymphomas, myelomas, Hodgkins disease). These AML occur after a latent period of a few years. They may present with myelodysplastic features evolving rapidly to AML. Until recently these were assumed to be exclusively the result of administration of alkylating agents. These AML are frequently associated with acquired chromosomal abnormalities involving 5q, -7/del(7q) and other complex rearrangements, and more rarely with translocations. The morphological presentation and cytogenetic features of these two first types of "secondary" AML (sAML) are somewhat similar to "multilineage AML" (mAML). , 
  • Another situation that has been described more recently is AML developing after the administration of agents that bind to DNA-topoisomerase II. In contrast to the loss of chromosomal material after alkyliting agent exposure, balanced translocations ("de novo" type AML): 11q23, usually t(9;11), or 21q22, t(8;21) or even t(15;17) have been noted in these leukemias. This category has a morphologic presentation similar to the corresponding "de novo" AML and a much more favorable outcome with chemotherapy. , Morphologically, the diagnosis of AML is based on the cytological aspect of the blast cells and the maturation of the different cell lineages in bone marrow aspirate, in addition to quantitative parameters obtained from the peripheral blood. Blood films, although essential, are not considered sufficient for diagnosis. The major criteria required for sub-classification are based on bone marrow aspirates. This explains the care required in difficult cases, in which the bone marrow aspirate is hypocellular. In these cases, as well as those with myelofibrosis, precise diagnosis needs the additional information of histological examination of a bone marrow biopsy. When the bone marrow is hypercellular or normocellular and easy to aspirate, bone marrow biopsy is usually not essential and cytological examination of smears is sufficient. With some reservations the sub-classification criteria can also be used for the material from patients with relapsing acute leukemia.
     , MORPHOLOGICAL CATEGORIES. The categories of this fourth group reflect the previous FAB classification with eight main types of AML (from M0 to M7 AML) and one additonal category for the so-called "biphenotypic AL". AML M1 and M2 show predominantly granulocytic (neutrophil) differentiation. Very specific hypergranular cells characterize M3 AML. AML M4 and M5 both show monocytic differentiation, predominantly monocytic for M5, and mixed monocytic-granulocytic for M4. Predominantly erythroblastic and megakaryoblastic differentiation are characteristic of AML M6 and M7 AML respectively; the myeloid nature of M0 is defined only on immunological markers (myeloid and no lymphoid markers) in patients lacking morphological or cytochemical criteria for AML. Biphenotypic acute leukemias are defined for patients having both lymphoid and myeloid immunological markers.
  • Cytogenetics

    t(8;21)(q22;q22)

    DEFINITION: The translocation t(8;21)(q22;q22) is one of the most common structural aberration in acute myeloid leukemia and is found in 5-12% of AML and in one-third of karyotypically abnormal M2 cases according to the French-American-British (FAB) classification.
    MORPHOLOGY AND CYTOCHEMISTRY: Among the non-random chromosomal aberrations observed in AML, t(8;21)(q22;q22) is one of the best known and usually correlates with AML M2, with well defined and specific morphological features. AML M2 FAB is the morphological type predominating in correlation with t(8;21), but some AML M1 or AML M4 cases have been also reported. Rare cases with a low bone marrow blast cell count (<20%) may be distinguished to RAEB and should be include in the AML group with low blast cell count category (see below). AML M2 with t(8;21) are more common in children than adults.
    IMMUNOLOGICAL MARKERS: M2 AML with t(8;21) show frequent co-expression of the B lymphoid marker CD19 with CD33 and CD34 and less often CD56.
    CLINICAL FEATURES: t(8;21) is usually associated with a good response to chemotherapy and a high remission rate with long-term disease-free survival. A large number of patients demonstrate additional chromosome abnormalities: loss of sex chromosome and del(9)(q22); no adverse outcome have been noted for either additional abnormality.Tumoral manifestation such as bony chloromas, may be seen at presentation; in such cases the initial bone marrow aspiration may show a limited and misleadingly low number of blast cells. These should not be confused with MDS. In these particular cases, AML M2 can still be diagnosed even if the morphological features described above are present, although the blasts are below 20% (see below).
    MOLECULAR ANALYSIS: Both heterodimeric components of the core binding factor complex (CBF), CBFalpha (also known as AML1) and CBFbeta are known to be involved in translocations associated with leukemia. The translocation t(8;21)(q22;q22) involves the AML1 (21q22) and ETO (8q22) genes. The AML/ETO - fusion transcript is consistently detected in patients with t(8;21) AML. Disruption of the AML1 gene is clustered within a single intron. AML1 has similarities to the drosophilia segmentation gene RUNT. Some AML M2 patients with the cytological profile described above, demonstrate rearrangement of AML1 and ETO despite being cytogenetically negative for the 8;21 translocation.

    inv/del(16)(p13q22)/del(16)(q22)/t(16;16)(p13;q22)

    DEFINITION: Patients with inv(16)(p13q22) usually correspond to the subclass of AML M4, with a specific abnormal eosinophil component and is considered as a distinct entity in correlation with these specific chromosomal abnormalities. These cases of AML M4 are referred as AML M4EO.
    MORPHOLOGY AND CYTOCHEMISTRY: In addition to the morphological features of AML M4, the bone marrow shows a variable number of eosinophils at all stages of maturation without significant maturation arrest. The most strinking abnormalities involve the immature eosinophilic granules. Whilst the majority of inv(16)(p13q22) have been identified as AML M4EO, this abnormality may occasionally been seen in other myeloid malignancies, including AML M2, M4 without eosinophilia, M5 and MDS.
    IMMUNOPHENOTYPE: Although no specific markers for the monocytic cell line have been identified, some positive markers such as CD14, CD15, CD4, CD11b and CD11c in addition to CD13 and CD33 may be a good indication for monocytic differentiation. In M4 AML with inv(16), co-expression of CD2 with myeloid markers have been demonstrated.
    CLINICAL FEATURES: Convergent studies has revealed that patients with M4 AML with inv(16) and t(16;16) achieved higher complete remission (CR) rates. Conversely del(16q) is different and do not have a better outcome than other M4 AML or MDS. It remains to be defined whether CBFbeta is involved in these deletions.
    MOLECULAR ANALYSIS: Inv(16) and t(16;16) both result in the fusion of the CBFbeta gene at 16q22 to the smooth muscle myosin heavy chain ( MYH11) at 16p13. CBFbeta codes for Core Binding Factor (CBFbeta) sub-unit, a heterodimeric transcription factor known to bind the enhancers of various murine leukemia viruses and similar motifs in the regulatory regions of T cell (TCR), myeloperoxidase, neutrophil elastase and several growth factor receptor gene. The CBFbeta sub-unit is identical to AML1, one of the gene involved in the t(8;21) translocation usually associated with AML M2. Occasionally cytological features of AML M4EO may be present without karyotypic evidence of abnormality of chromosome 16. The CBFbeta/MYH11 is usually demonstrated by molecular studies. Thus, at diagnosis, the use of FISH and RT-PCR methods are important when evaluating inv(16).

    t(15;17)(q22;q21)

    DEFINITION: t(15;17)(q22;q21) is associated consistently with M3 AML. This chromosomal abnormality first appeared to be confined to the characteristic or morphologically typical M3 AML or "hypergranular promyelocytic leukemia", defined by bone marrow replacement with highly granulated blast cells, with occasional pseudo Pelger-Huet cells
    MORPHOLOGY AND CYTOCHEMISTRY. The nuclear size and shape is irregular and highly variable; they are often kidney-shaped or bilobed.The cytoplasm is completely occupied by densely packed or even coalescent granules, staining bright pink, red or purple by MGG. In some cells the cytoplasm is filled with fine dust-like granules. Characteristic cells contain bundle of Auer rods ("faggot cells"). In M3 AML, MPO is always strongly positive in all blast cells. Cases with a similar t(15;17) but with different morphological features, have been subsequently reported and have been called alternatively "M3-variant" AML, or "microgranular" variant. Distinct morphological features such as paucity or absence of granules, and a prominently bilobed nuclear shape characterize them.
    IMMUNOLOGICAL MARKERS: M3 AML with t(15;17) is usually characterized by the association of the lymphoid marker, CD2 and CD19, with myeloid markers and the negativity of HLA-DR and CD34.
    CLINICAL FEATURES: M3/M3-variant AML is frequently associated with disseminated intra-vascular coagulation (DIC). A particular sensitivity to treatment with all-trans retinoic acid (ATRA) has been demonstrated. ATRA act as a differentiation therapy for acute promyelocytic leukemia. The prognostic value of M3 AML/t(15;17) is inferior to t(8;21) and inv(16) and superior to the poor prognostic group (AML with abnormalities of the chromosomes 5 and 7). AML M3 patients are however increasingly treated in independent protocols, rendering such comparison difficult.
    MOLECULAR ANALYSIS: The sensitivity of M3 cells to all-trans retinoic acid led to the discovery that the retinoic acid receptor alpha ( RARalpha) gene on 17q21 fuses with a zinc finger binding transcription factor on 15q22 (promyelocytic leukemia or PML) gene, thus giving rise to a PML-RARalpha fusion gene product. Chromosomal variant of t(15;17). Rare cases lacking the classical t(15;17) have been described either having complex variant translocations involving both chromosomes 15 and 17 with additional chromosome(s), expressing in all studied cases, the PML/RARalpha transcript, or cases where neither chromosome 15 nor chromosome 17 are apparently involved, but with submicroscopic insertion of RARalpha into PML leading to expression of the PML/RARalpha transcript; these latter cases are considered as cryptic or masked t(15;17). Morphological analysis showed no major difference between the t(15;17) positive control group and the PML/RARalpha positive patients without t(15;17).

    t(11;17)(q23;q21)

    DEFINITION: Several AML cases with translocation t(11;17)(q23;q21), in which the promyelocytic leukemia zinc finger ( PLZF) gene is translocated to RARalphagene on 17q21 have been reported. This finding that the RARalpha gene is involved in both t(15;17) and t(11;17) suggests the importance of the modified RARalpha in AML.
    MORPHOLOGY AND CYTOCHEMISTRY: Patients were initially reported as having M3 morphology. Interestingly, the t(11;17)(q23;q21) PLZF/RARalpha subgroup showed clearly morphological differences with predominance of cells with regular nuclei, many granules, usually no Auer rods, increased number of pseudo Pelger-Huet cells and a strong MPO activity. These particular characteristics could allow the definition of a separate morphological entity among APL.
    CLINICAL FEATURES: M3-like patients with t(11;17)(q23;q21) are resistant to ATRA, both in vivo and in vitro.
    MOLECULAR ANALYSIS: In patients with t(11;17)(q23;q21), where RARalpha is fused to the PLZF (promyelocytic leukemia zinc finger) gene, chromosome 17 and RARalpha but not PML are involved.

    11q23

    DEFINITION: Molecular studies have identified a human homologue of the drosophila trithorax gene (designed HRX or MLL). MLL is a developmental regulator and is structurally altered in leukemia associated translocations that show an abnormality at band 11q23.
    MORPHOLOGY AND CYTOCHEMISTRY: There is a strong association between AML M5/M4 and deletion and translocations involving 11q23. Sometimes cases of 11q23 M5B and M4, and occasionally M2 or M1 also show MLL rearrangement. Two clinical subgroups of patients have a high frequency of 11q23 aberration and M5 subtypes: one is AML in infants with MLL rearrangement in about 50% of cases; the other group is "secondary leukemia" (sAML) potentially after treatment with DNA topoisomerase II inhibitors. In general the translocations in these leukemia are the same as those occurring in "de novo" leukemia i.e.t(9;11), t(11;19).
    MOLECULAR ANALYSIS: The MLL gene on 11q23 is involved in a number of translocations with different partner chromosomes. The most common translocations observed in childhood AML are the t(9;11)(p21;q23) and the t(11;19)(q23;p13.1); other translocations of 11q23 involve at least 50 different partners chromosomes. A partial tandem duplication of MLL gene has also been reported in the majority of adult patients whose leukemic blast cells have a +11 and in some with normal karyotype. Molecular studies have shown that MLL is rearranged more frequently than is revealed by conventional cytognetic studies.

    Disease

    Second group WHO: mAML : Multilineage AML

    Note

    DEFINITION: This category is defined by the presence of multilineage dysplasia on cytological analysis. In contrast to the patients with "recurrent translocation", "multilineage AML" by definition involve all myeloid cell lineages. This category of AML occurs mainly in elderly patients and is rare in children. Translocations typical of "de novo AML" in young patients are not found in "multilineage AML". Dysplasia may be analyzed according to standard criteria (presence in >50% of each cell category). Granulocytic dysplasia (DysG) may be defined as polymorphonuclear neutrophils (PMN) with agranular or with hyposegmented nuclei (pseudo Pelger-Huet anomaly). Dysplastic features of erythroblastic precursors define Erythroid dysplasia (DysE): (megaloblastic or macroblastic aspects, karyorexis, nuclear fragments or multinuclearity). Megakaryocytic dysplasia (DysM) may be diagnosed when micromegakaryocytes, large megakaryocytes with monolobed or with multiple separated nuclei are found. A special mention has to be made of the high frequency of dysmegakaryopoiesis and the utmost importance of clearly separating abnormal megakaryocytic cells with normal ploidy and non lobed ("monolobed") nuclei from hypoploid ("micromegakaryocytes") megakaryocytes and from megakaryocytes with multiple separated nuclei.

    Cytogenetics

    KARYOTYPIC/MOLECULAR ANALYSIS: In this group of patients chromosomes abnormalities include gain or loss of major segments of chromosomes: -5, -7/del(7q), +8, +9, +11, del(11q), del(12p), del(17p), -18, +19, del(20q), +21 and less often specific translocations t(2;11), t(1;7)(q10;p10) and translocations involving 3q21 and 3q26.

    Disease

    Third group WHO: "Secondary AML"

    Note

    DEFINITION The term "secondary" AML has been utilized to encompass several different situations.

    Disease

    Fourth group WHO: Morpholocical and Immunophenotyping classification

    Note

    DEFINITION: A morphological and immunophenotypic classification remains necessary for the other situations which do not fit with the two preceding main categories, respectively: "recurrent translocations AML" (so-called "de novo") and "multilineage AML".

    Highly cited references

    Pubmed IDYearTitleCitations
    357385932022Clinical Impact of Platelet-to-albumin Ratio on Esophageal Cancer Patients Who Receive Curative Treatment.0
    357368432022Nurses' knowledge of and attitude to nursing information systems.0
    357366312022Cancer treatment and survivorship statistics, 2022.0
    357365672022Assessment of left ventricular myocardial work done by noninvasive pressure-strain loop technique in patients with essential hypertension.0
    357340092022Portable digital X-ray for TB pre-diagnosis screening in rural communities in Nigeria.0
    357331752022Exploring the potential mechanism of emetine against coronavirus disease 2019 combined with lung adenocarcinoma: bioinformatics and molecular simulation analyses.0
    357324972022Expanding the phenotype of ATP6AP1 deficiency.0
    357314462022Single-incision clipless laparoscopic total colectomy for intractable slow transit constipation: a single surgeon's experience.0
    357290202022Advantages of peripheral blood stem cells from unrelated donors versus bone marrow transplants in outcomes of adult acute myeloid leukemia patients.0
    357289022022Validation of a delirium predictive model in patients admitted to surgical intensive care units: a multicentre prospective observational cohort study.0
    357154682022Freezing solute atoms in nanograined aluminum alloys via high-density vacancies.0
    357154362022Dissolved oxygen isotope modelling refines metabolic state estimates of stream ecosystems with different land use background.0
    357257822022The effect of SARS-CoV-2 vaccination on post-acute sequelae of COVID-19 (PASC): A prospective cohort study.0
    357229682022Further description of the Kerguelen sandpaper skate Bathyraja irrasa (Rajiformes: Arhynchobatidae) based on additional specimens including egg cases and embryos.0
    357209882022Synthesis of MeOH and DME From CO2 Hydrogenation Over Commercial and Modified Catalysts.0
    357202972022GMZ2 Vaccine-Induced Antibody Responses, Naturally Acquired Immunity and the Incidence of Malaria in Burkinabe Children.0
    357198822022Resizing the largest known extinct rodents (Caviomorpha: Dinomyidae, Neoepiblemidae) using occipital condyle width.0
    357191612022Structural Characterization, Antioxidant and Antibacterial Activities of a Novel Polysaccharide From Zingiber officinale and Its Application in Synthesis of Silver Nanoparticles.0
    357188462022Stroke admissions during the COVID-19 pandemic: a single-center retrospective analysis.0
    357182022022Outcomes of Biventricular and Single Ventricle Heterotaxy Patients: A Single Center 5-Decade Experience.0
    357172052022Oncogenic functions and clinical significances of DCLK1 isoforms in colorectal cancer: a systematic review and meta-analysis.0
    357146482022Incidence of typhoid and paratyphoid fever in Bangladesh, Nepal, and Pakistan: results of the Surveillance for Enteric Fever in Asia Project.0
    357137382022Consensus on the criteria for patient prioritization in hospital clinical pharmacy services: a Delphi study.0
    357133592022Deep-learning synthesized pseudo-CT for MR high-resolution pediatric cranial bone imaging (MR-HiPCB).0
    357116892022The Underlying Molecular Basis and Mechanisms of Venous Thrombosis in Patients with Osteomyelitis: A Data-Driven Analysis.0
    357098272022Clinical Outcomes of Repeated Radioactive Iodine Therapy for Graves' Disease.0
    357095552022Effects of dietary crude protein concentration on animal performance and nitrogen utilisation efficiency at different stages of lactation in Holstein-Friesian dairy cows.0
    357081322022N-Hydroxy-N-oxide photoinduced tautomerization and excitation wavelength dependent luminescence of ESIPT-capable zinc(II) complexes with a rationally designed 1-hydroxy-2,4-di(pyridin-2-yl)-1H-imidazole ESIPT-ligand.0
    357009192022Global, regional, and national childhood cancer burden, 1990-2019: An analysis based on the Global Burden of Disease Study 2019.0
    357004042022Operative Versus Nonoperative Management of Displaced Midshaft Clavicle Fractures: A Cost-effectiveness Analysis.0
    356982092022Patterns of multidrug resistant organism acquisition in an adult specialist burns service: a retrospective review.0
    356918412022Effects of Deodorization on the Formation of Processing Contaminants and Chemical Quality of Sunflower Oil.0
    356912192022Knowledge and attitudes towards epilepsy: A survey of people with epilepsy.0
    356795912022Hierarchical-Structured Pd Nanoclusters Catalysts x-PdNCs/CoAl(O)/rGO-T by the Captopril-Capped Pd Cluster Precursor Method for the Highly Efficient 4-Nitrophenol Reduction.0
    356753132022Association between Meat, Fish, and Fatty Acid Intake and non-Hodgkin Lymphoma Incidence: the Japan Public Health Center-Based Prospective Study.0
    356741222022Long-term effectiveness of Self-Help Plus in refugees and asylum seekers resettled in Western Europe: 12-month outcomes of a randomised controlled trial.0
    356738742022The longest mitochondrial protein in metazoans is encoded by the male-transmitted mitogenome of the bivalve Scrobicularia plana.0
    356721012022Medical optimization of the peripheral artery disease patient.0
    356719312022Patients with Limited Health Literacy Have Worse Preoperative Function, Pain Control and Experience Prolonged Hospitalizations Following Shoulder Arthroplasty.0
    356674322022Acid-mediated hydrothermal treatment of sewage sludge for nutrient recovery.0
    356666052022Potentiality of impulse oscillometry to evaluate bronchodilator reversibility in untreated adult patients with newly diagnosed asthma.0
    356666032022Effect of Different Roasting Conditions and Coreopsis Extract on the Heterocyclic Amine Formation in Roast Lamb Products.0
    356663872022Spatial-Temporal Analysis of Factors Influencing the Median Urine Iodine Concentration of 8-10-year-old Children in Xinjiang, China 25 Years after Implementation of the Salt Iodization Policy.0
    356659302022Association between periodontitis and peripheral markers of innate immunity activation and inflammation.0
    356616012022Increasing the lycopene content and bioactive potential of tomato fruits by application of encapsulated biological and chemical agents.0
    356614892022Low molecular weight heparin and pregnancy outcomes in women with inherited thrombophilia: A systematic review and meta-analysis.0
    356603842022Self-reported Frailty Screening Tools: Comparing Construct Validity of the Frailty Phenotype Questionnaire and FRAIL.0
    356530262022Identification of conserved regions from 230,163 SARS-CoV-2 genomes and their use in diagnostic PCR primer design.0
    356530102022Efficacy and Safety of Fluoroscopy-Guided Self-Expandable Metal Stent Placement for Treatment of Malignant Colorectal Obstruction.0
    356510732022Ultrasound accelerates pickling of reduced-sodium salted duck eggs: An insight into the effect on physicochemical, textural and structural properties.0
    356492472022Synthesis of Phase-Pure Thermochromic VO2 (M1).0
    356234722022Phenolic acids and their carboxylate anions: Thermodynamics of primary antioxidant action.0
    356231052022Effectiveness and safety of edoxaban therapy in daily-care patients with atrial fibrillation. Results from the DRESDEN NOAC REGISTRY.0
    356212002022Clinical Impact of Heart Team Decisions for Patients With Complex Valvular Heart Disease: A Large, Single-Center Experience.0
    355984362022Digitizing ECG image: A new method and open-source software code.0
    355927402022CB-RAF600E-1 exerts efficacy in vemurafenib-resistant and non-resistant-melanoma cells via dual inhibition of RAS/RAF/MEK/ERK and PI3K/Akt signaling pathways.0
    355890632022Consideration of metabolomics and transcriptomics data in the context of using avian embryos for toxicity testing.0
    355887712022Appraisal of different land use systems for heterotrophic respiration in a Karst landscape.0
    355886812022Unified validation of a refined second-generation HR-pQCT based homogenized finite element method to predict strength of the distal segments in radius and tibia.0
    355840102022Do Physical Therapy and Yoga Improve Pain and Disability through Psychological Mechanisms? A Causal Mediation Analysis of Adults with Chronic Low Back Pain.0
    355804702022Environmental and human health at risk - Scenarios to achieve the Farm to Fork 50% pesticide reduction goals.0
    355769562022Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.0
    355678152022Electrochemically deposition of metal-organic framework onto carbon fibers for online in-tube solid-phase microextraction of non-steroidal anti-inflammatory drugs.0
    355520692022What's sleep got to do with it? Longitudinal associations between insomnia, PTSD, and alcohol use among U.S. Veterans.0
    355273512022On the demand for telemedicine: Evidence from the COVID-19 pandemic.0
    355251822022Environmental sustainable mathematically processed UV spectroscopic methods for quality control analysis of remogliflozin and teneligliptin: Evaluation of greenness and whiteness.0
    355091772022Total and regional body adiposity increases during menopause-evidence from a follow-up study.0
    354896982022Interaction analysis of FADS2 gene variants with chronic hepatitis B infection in Chinese patients.0
    354725602022Human biomonitoring of persistent and non-persistent pollutants in a representative sample of the general population from Cape Verde: Results from the PERVEMAC-II study.0
    354518582022Changes in acute headache medication use and health care resource utilization: Results from a randomized, double-blind, placebo-controlled clinical trial evaluating galcanezumab in adults with treatment-resistant migraine (CONQUER).0
    354471772022Non-targeted screening of volatile organic compounds in a museum in China Using GC-Orbitrap mass spectrometry.0
    354375192022UV inactivation of Semliki Forest virus and E. coli bacteria by alternative light sources.0
    354293382022Healthy lifestyle index and the risk of ductal carcinoma in situ of the breast in the Women's Health Initiative.0
    354279872022Schmorl's nodes could be associated with intervertebral disc degeneration at upper lumbar levels and end-plate disease at lower lumbar level in patients with low back pain.0
    354170332022Expression of cellular retinoic acid binding protein 1 predicts peritoneal recurrence of gastric cancer.0
    354108422022Development of competencies for advanced nursing practice in intensive care units across Europe: A modified e-Delphi study.1
    353794722022Outcomes after ORIF of Bicondylar Schatzker VI (AO type C) Tibial Plateau Fractures in an Elderly Population.0
    353786872022Relationship of Location Between Tear Film Center and Corneal Vertex Following Small-Incision Lenticule Extraction.0
    353779622022Fiducial marker position affects target volume in stereotactic lung irradiation.0
    353675282022Low-dose Radiation Therapy in the Management of COVID-19 Pneumonia (LOWRAD-Cov19). Final results of a prospective phase I-II trial.0
    353665242022Study on the origin of linear deviation with the Beer-Lambert law in absorption spectroscopy by measuring sulfur dioxide.0
    353629162022Long-term Impact of Laparoscopic Sleeve Gastrectomy on Drug Costs of Japanese Patients with Obesity and Type 2 Diabetes Mellitus.0
    353554412022Clinical characteristics and frailty status in heart failure with preserved vs. reduced ejection fraction.1
    353537982022Identification of rare mutations of the vasoactive intestinal peptide receptor 2 gene in schizophrenia.0
    353440352022Phase II Multi-institutional Clinical Trial Result of Concurrent Cetuximab and Nivolumab in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma.0
    353433492022Evaluation of tenofovir disoproxil fumarate loaded silver nanoparticle on testicular morphology in experimental type-2 diabetic rats.0
    353335942022Comparative study of conventional ROI-based and volumetric histogram analysis derived from CT enhancement in differentiating malignant and benign renal tumors.0
    353256292022Effect of mineral fertilisers application on the transfer of natural radionuclides from soil to radish (Raphanus sativus L.).0
    353051522022Sequential optimization strategy for the immobilization of Erwinia sp. D12 cells and the production of isomaltulose with high stability and prebiotic potential.0
    352906852022Effect of the implant-supported provisional restoration on the accuracy of digital peri-implant mucosa replication-A clinical study.0
    352498432022Linguistic Differences by Gender in Letters of Recommendation for Minimally Invasive Gynecologic Surgery Fellowship Applicants.0
    352392472022Neurological outcomes 1 year after COVID-19 diagnosis: A prospective longitudinal cohort study.1
    352315082022Agricultural flood vulnerability assessment and risk quantification in Iowa.0
    352026882022Direct conversion of almond waste into value-added liquids using carbon-neutral catalysts: Hydrothermal hydrogenation of almond hulls over a Ru/CNF catalyst.0
    351763812022Balancing acidogenesis and methanogenesis metabolism in thermophilic anaerobic digestion of food waste under a high loading rate.0
    351722112022Shoulder kinematics and muscle activity following latissimus dorsi transfer for massive irreparable posterosuperior rotator cuff tears in shoulders with pseudoparalysis.0
    351661512022Interictal plasma endothelin-1 levels do not change in individuals with episodic and chronic migraine.0
    351345572022Synthetic metabolic pathways for conversion of CO2 into secreted short-to medium-chain hydrocarbons using cyanobacteria.0
    351328152022Sodium-glucose cotransporter 2 inhibitors do not increase the risk of fractures in real-world clinical practice in Korea: A national observational cohort study.0
    351287032022Impurity-profiling UPLC methods for quantitative analysis of some antiemetics formulated with pyridoxine.0

    Bibliography

    Pubmed IDLast YearTitleAuthors
    31639331988Morphologic, immunologic and cytogenetic (MIC) working classification of the acute myeloid leukaemias. Second MIC Cooperative Study Group.
    1884401976Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group.Bennett JM et al
    105778571999World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997.Harris NL et al

    Summary

    Note

    Basis of classification in conformity with WHO recommandations.

    The classification of acute myeloid leukemia (AML) and myelodysplasic syndromes (MDS) includes clinical data (previous history, age) and biologic characteristics (morphology, cytochemistry, immunophenotype, cytogenetic and molecular biology). The separation of homogeneous classes allows us to distinguish pronostic parameters and to identify groups of patients sensitive to drugs or to specific treatment. Recurrent cytogenetic abnormalities are strong prognostic indicators in AML and MDS. Molecular studies of structural chromosomal changes have enabled the cloning of genes located at chromosomal breakpoints and have helped to characterize the proteins involved in leukemogenesis. Morphologic studies remain important because of a strong correlation with cytogenetic and molecular abnormalities.

    The clinico-biological classification of acute myeloid leukemia (AML) should include morphological, cytochemical, immunophenotypic, cytogenetic and molecular characterization of the leukemia blasts. The identification of homogeneous categories would allow the development and refinement of treatment strategies.
    - Recurrent cytogenetic abnormalities are important as prognostic indicators in AML. The identification of specific abnormalities is used increasingly to decide treatment. Cytogenetic findings have contributed to the understanding of morphological and clinical heterogeneity of AML. Molecular genetic analysis of recurrent translocations and inversions has led to clone genes adjacent to chromosome breakpoint and to characterize their protein products involved in the leukemogenesis process.
    - Over the years, leukemia classifications have been mainly descriptive, which was open to regular criticism, revision and reassessment. During the last 20 years, classification according to morphological features of leukemia has been proposed (F.A.B. defined classification). This classification is based on cell morphology on May-Grunwald-Giemsa (MGG) staining of peripheral blood and bone marrow smears with the addition of simple cytochemical techniques

    Rationale for a new classification approach
    - The age-incidence of AML is subtly bimodal. Between early childhood and age 45, the annual incidence of acute myeloid leukemia (AML) remains constant at 0.8 cases/105population. The incidence rises exponentially after the age of 45, exceeding 15 cases/105 population by age 75. AML has been extensively characterized using cytogenetic since the mid-1970s.
    - Available data have suggested an alternative classification in four main groups; a first one for patients identified with specific balanced translocations, the second group for patients with "multilineage" deregulation, a third one for "secondary" AML (after exposure to mutagenic agent or chemo/radiotherapy). Although this is a more rational model of AML classification, some patients cannot be classified into the three first groups and defined a fourth group. At least for the moment, the diagnosis of this last group of patients must rely on the classical cytologic approach (FAB) defining "morphological"-based category.

  • The first group is characterized by recurring chromosomal abnormalities, mainly balanced reciprocal translocations and affects children and young adults. In this group, it is assumed that there is involvement of committed precursor. This may explain the cellular involvement of a specific subset of myeloid cells for example pure granulocytic cells in t(15;17) AML, granulocytic and eosinophilic cells in t(8;21) AML, and monocytes and eosinophils in inv(16). These patients often have a high rate of complete remission with cytotoxic chemotherapy.
  • The second group has similar abnormalities to those which are associated with myelodysplastic syndromes, occur mainly in the elderly population and are rare in childhood. They are characterized by multilineage involvement of bone marrow cells suggesting an early commitment precursor (stem cell). Cytogenetic studies usually show complex chromosome aberrations, mainly loss of genetic material. These diseases are associated with a poor prognosis and a lesser incidence of complete remission after chemotherapy.
  • The third group concerns "secondary" AML (mainly after treatment for malignant diseases) usually morphologically and cytogenetically related with the second group, or more rarely with the first one, depending of the type of triggering drug used.
  • Citation

    Georges Flandrin

    Classification of acute myeloid leukemias

    Atlas Genet Cytogenet Oncol Haematol. 2002-05-01

    Online version: http://atlasgeneticsoncology.org/haematological/1238/classification-of-acute-myeloid-leukemias

    External Links