Classification of B-cell chronic lymphoproliferative disorders (CLD)

2000-02-01   Antonio Cuneo 

1.Hematology Section, Dept. Of Biomedical Sciences, University of Ferrara, 44100 Ferrara Italy

Clinics and Pathology


Chronic lymphocytic leukemia CD5+ B cell that has encountered the antigen and harbours hypermutated IgV genes

Phenotype stem cell origin

CD5+; CD23+; CD38+/-; CD22 weak+; FMC7-; sIg+ weak , 
  • Pan-B+; CD5-/+; CD23-/+; CD11c+/-; CD25-/+; FMC7+/-; sIg+ bright
  • Cytogenetics

    del(13q) (10-15% of the cases): Typical morphology; indolent disease; favourable prognosis if present as the sole change (Note: typical morphology (FAB criteria): more than 90% of neoplastic cells are represented by small lymphocytes (diameter less than 14 m, i.e. < two red blood cells); atypical morphology: 10-55% of the lymphocytes are larger than 14 m with few prolymphocytes (CLL mixed-cell type); the cases are usually referred to as CLL/PL if prolymphocytes predominate among large lymphoid cells; PLL: more than 55%, and usually >70% of the cells are prolymphocytes.) , 
  • (20-40% of cases) with or without +3 , 
  • t(11;14)(q13;q32) ( involved, mainly in the MTC and mTC1)(<5% of the cases): Rare cases of CLL/PL, transforming into prolymphocytic leukemia; Primary blood and marrow involvement, usually with splenomegaly, without adenopathy
  • Disease

    Chronic lymphocytic leukemia CD5+ virgin recirculating B-cell with germline IgV genes

    Phenotype stem cell origin

    CD5+; CD23+; CD38-/+; CD22 weak+; FMC7-; sIg+ weak


    +12 (10-15% of the cases): Frequent atypical morphology; relatively indolent disease; unfavourable prognosis as compared with other single chromosome aberrations, but not against complex karyotypes, 11q- or 17p-.


    Chronic lymphocytic leukemia CD5+ recirculating B-cell

    Phenotype stem cell origin

    CD5+; CD23+; CD22 weak+; FMC7-; sIg+ weak


  • (20% of the cases) (breaks outside the MTC and mTC1 of BCL1)
  • Phenotype stem cell origin

    Peripheral B-lymphocyte that has encountered the antigen and harbours hypermutated IgV genes


    Rare and aggressive disease with a majority of relatively large lymphocytes with round nucleus and a prominent central nucleolus


    t(11;14)(q13;q32) (BCL1 involved in the MTC and mTC1)

    Phenotype stem cell origin

  • Marginal zone lymphocytes harbouring hypermutated IgV genes
  • Clinics

    Indolent disease; There are not establisehd correlations between chromosome lesions and hematologic features; Cases with t(11;14) showed frequent CD5-positivity and featured an indolent course

    Highly cited references

    Pubmed IDYearTitleCitations
    357176172022Association between socioeconomic factors and origin of hospital referrals among patients with oral cancer.0
    357141162022Increased risk of venous thromboembolism in patients with granulomatosis with polyangiitis: A population-based study.0
    357112872022Daily and hourly patterns of physical activity and sedentary behavior of older adults: Atherosclerosis risk in communities (ARIC) study.0
    357100452022Spectrum and Prevalence of Side Effects and Complications with Guideline Directed Therapies for Congenital Long QT Syndrome.0
    357091612022Risk factors for multidrug-resistant tuberculosis: A worldwide systematic review and meta-analysis.0
    357090342022Ultra-compact diode-pumped single-frequency Ti:sapphire laser.0
    356920252022[Etiological analysis of infectious keratitis in children from 2007 to 2016].0
    356800192022Prevalence of SWI/SNF genomic alterations in cancer and association with the response to immune checkpoint inhibitors: A systematic review and meta-analysis.0
    356785562022A highly sensitive colorimetric sensing platform based on silver nanocomposites for alkaline phosphatase.0
    356723772022A neuronal social trait space for first impressions in the human amygdala and hippocampus.0
    356684202022Observational study of population genomic screening for variants associated with endocrine tumor syndromes in a large, healthcare-based cohort.0
    356624742022Prevalence of Coronary Artery Anomalies in Young and Middle-Aged Sudden Cardiac Death Victims (from a Prospective State-Wide Registry).0
    356614152022Melanosis coli: A factor not associated with histological progression of colorectal polyps.0
    356592882022Long-term observation after transplantation of cultured human corneal endothelial cells for corneal endothelial dysfunction.0
    356586362022Workplace environmental exposure level guide: n-Methyl-2-pyrrolidone.0
    356579942022Self-reported physical activity and different cardiovascular diseases-Results from updated measurements over 40 years.0
    356568132022Effect of Renin-Angiotensin-Aldosterone System Inhibitors on the Rupture Risk Among Hypertensive Patients With Intracranial Aneurysms.0
    356560532022Role of ABO Blood Groups in Susceptibility and Severity of COVID-19 in the Georgian Population.0
    356553412022Dual-Atom Nickel Moieties of Ni(II)2 N4 (µ2 -N)2 Anchored on Alfalfa-Derived Developed Porous N-Doped Carbon for High-Performance Li-S Battery.0
    356483042022Usage of procalcitonin and sCD14-ST as diagnostic markers for postoperative spinal infection.0
    356480642022Minimal Clinically Important Changes in HOOS-12 and KOOS-12 Scores Following Joint Replacement.0
    356169982022Rational Design of Bisphosphonate Lipid-like Materials for mRNA Delivery to the Bone Microenvironment.0
    355970032022Standing out or fitting in: A latent projective content analysis of discrimination of women and 2SLGBTQ+ anesthesiologists and providers.0
    355768442022A simple assessment model based on phase angle for malnutrition and prognosis in hospitalized cancer patients.0
    355131132022Associations of long-term exposure to ambient air pollution and road traffic noise with sleep health in UK Biobank.0
    354772992022Microwave-Assisted Synthesis of Red Emitting Copper Nanoclusters Using Trypsin as a Ligand for Sensing of Pb2+ And Hg2+ Ions in Water and Tobacco Samples.0
    354677682022What would it take to convince you to donate? A survey study of the relationship between motivators, barriers, and payment for whole blood, plasma, and platelet donation.0
    354663262022Usage of nutritional supplements to improve immunity during the COVID-19 pandemic: An online survey.0
    354302362022Semantic flow and its relation to controlled semantic retrieval deficits in the narrative production of people with aphasia.0
    354265412022Value of the 21-gene expression assay in predicting locoregional recurrence rates in estrogen receptor-positive breast cancer: a systematic review and network meta-analysis.0
    354107432022Strongly Focused HIFU Transducers With Simultaneous Optical Observation for Treatment of Skin at 20 MHz.0
    353969822022Cost-effectiveness of exome and genome sequencing for children with rare and undiagnosed conditions.0
    353899442022Composite CYP3A phenotypes influence tacrolimus dose-adjusted concentration in lung transplant recipients.0
    353790812022The global lung function initiative 2021 (GLI-2021) norms provide mixed results for static lung volumes (SLVs) in Algerian adults.0
    353777132022Changes in Health Care Spending, Use, and Clinical Outcomes After Nonfatal Firearm Injuries Among Survivors and Family Members : A Cohort Study.0
    353588852022Corrigendum to "Development of antibacterial and high light transmittance bulk materials: Incorporation and sustained release of hydrophobic or hydrophilic antibiotics" [Colloids Surf. B Biointerfaces 141 (2016) 483-490].0
    353570672022High-risk liver transplant recipients with grade 3 acute on chronic liver failure should receive the good quality graft.0
    353036392022Triple-emission nitrogen and boron co-doped carbon quantum dots from lignin: Highly fluorescent sensing platform for detection of hexavalent chromium ions.0
    352763392022Prevalence and genetic characterization of bovine coronavirus identified from diarrheic pre-weaned native Korean calves from 2019 to 2021.0
    352572292022Immunoglobulin substitution in patients with secondary antibody deficiency in chronic lymphocytic leukemia and multiple myeloma: a representative analysis of guideline adherence and infections.0
    351314982022Porous hetero-structured nickel oxide/nickel phosphide nanosheets as bifunctional electrocatalyst for hydrogen production via urea electrolysis.0
    350135262022Prognostic and predictive value of the newly proposed grading system of invasive pulmonary adenocarcinoma in Chinese patients: a retrospective multicohort study.0
    346354102022Learning curve for total thoracoscopic lobectomy for treating pediatric patients with congenital lung malformation.0
    357325062022Modulating Fingolimod (FTY720) Anti-SARS-CoV-2 Activity Using a PLGA-Based Drug Delivery System.0
    357302192022[Clinical characteristics and cost-effectiveness of intramedullary nail and plate for the treatment of open tibial fractures].0
    357272322022Causal Association between Whole Body Water Mass and Sleep Apnea: A Mendelian Randomization Study.0
    357144992022Anxiety and depression mood disorder in patients with nasal septal deviation: A systematic review and meta-analysis.0
    357140992022Depression and work productivity: insights from a longitudinal cohort study on digital care programs for Musculoskeletal conditions.0
    357111212022Correlation Analysis between Tibial Tuberosity-Trochlear Groove Distance and Other Patellar Stability Parameters in Young and Middle-aged Populations.0
    357078652022Neutrophil gelatinase-associated lipocalin: a biochemical marker for acute kidney injury and long-term outcomes in patients presenting to the emergency department.0
    357044372022Comparison of Blood Pressure and Vascular Health in Physically Active Late Pre- and Early Postmenopausal Females.0
    356968572022Schizotypy unfolding into the night? Schizotypal traits and daytime psychotic-like experiences predict negative and salient dreams.0
    356909162022Molecular characterization of insulin receptor (IR) in oriental fruit moth, Grapholita molesta (Lepidoptera: Tortricidae), and elucidation of its regulatory roles in glucolipid homeostasis and metamorphosis through interaction with miR-982490.0
    356865932022Relationship between Chewing Sugar-free Gum and Dental Caries Status in China.0
    356832812022Mechanically Robust Dual-Crosslinking Elastomer Enabled by a Facile Self-Crosslinking Approach.0
    356810532022Mendelian imputation of parental genotypes improves estimates of direct genetic effects.0
    356796702022Differences and variation in welfare performance of broiler flocks in three production systems.0
    356757102022Revisiting the Structure and Electrochemical Performance of Poly(o-phenylenediamine) as an Organic Cathode Material.0
    356744262022Effects of an alternative bleaching method for yerba mate leaves on total phenolic content: evaluation and prediction with soft-computing approaches.0
    356701042022End-of-life healthcare utilization and palliative care use among older adults with limited English proficiency.0
    356662192022First Report of Fusarium ipomoeae causing Fusarium wilt on Glycine max in South Korea.0
    356568912022Pharmacognostic standardization of Rhododendron afghanicum through scanning electron microscopy and analytical techniques.0
    356558412022Sagittal morphology of the cervical spine in adolescent idiopathic scoliosis: a retrospective case-control study.0
    356529212022[Digital health literacy of pupils. Level and associations with physical activity and dietary behavior].0
    356481962022Disproportionate Negative Career Impact of the COVID-19 Pandemic on Female Pediatric Cardiologists in the Northeast United States.0
    356367182022Occurrence, exposure and risk assessment of semi-volatile organic compounds in Chinese homes.0
    356177882022Design and operational considerations in response to Legionella occurrence in Las Vegas Valley groundwater.0
    355892822022A study into the nature and extent of drug driving recidivism in Queensland (Australia).0
    355678562022Interleukin-22 exacerbates angiotensin II-induced hypertensive renal injury.0
    355336202022Continuous monitoring of dissolved inorganic nitrogen (DIN) transformations along the waste-vadose zone - groundwater path of an uncontrolled landfill, using multiple N-species isotopic analysis.0
    355069972022Reliability of the Behaviorally Anchored Rating Scale (BARS) for assessing non-technical skills of medical students in simulated scenarios.0
    354770762022Association between parental mental illness and autoimmune diseases in the offspring - A nationwide register-based cohort study in Sweden.0
    354684252022Research Note: Interaction between hatching time and chick pull time affects broiler live performance.0
    354618722022Kigelia africana fruit biofibre polysaccharide extraction and biofibre development by silane chemical treatment.0
    354298572022A rapid fluorescence approach on differentiation of typical dinoflagellate of East China Sea.0
    354223142022The VA vascular injury study: A glimpse at quality of care in Veterans with traumatic vascular injury repair.0
    354043782022Postmortem Assessment of Olfactory Tissue Degeneration and Microvasculopathy in Patients With COVID-19.0
    353640222022Immunogenicity and safety of booster CYD-TDV dengue vaccine after alternative primary vaccination schedules in healthy individuals aged 9-50 years: a randomised, controlled, phase 2, non-inferiority study.0
    353415762022Hemodynamic and Clinical Determinants of Left Atrial Enlargement in Liver Transplant Candidates.0
    353317562022Predicting potential wildfire severity across Southern Europe with global data sources.0
    353055092022An omnidirectional piezoelectric transducer for selective excitation and reception of high-order shear horizontal waves.0
    352592722022RBC Folate and Serum Folate, Vitamin B-12, and Homocysteine in Chinese Couples Prepregnancy in the Shanghai Preconception Cohort.0
    351211632022In vitro activity of imipenem/releactam and comparator agents against clinical bacterial isolates from patients with cancer.0
    350160862022Identified needs of peripartum adolescents in Sub-Saharan Africa from 2013 to 2021: a mapping of domains for strengthening psychosocial interventions.0
    350141942022Estimating the burden of influenza-related and associated hospitalizations and deaths in France: An eight-season data study, 2010-2018.0
    349644912022Population Pharmacokinetics and Exposure-Response Relationships of Astegolimab in Patients With Severe Asthma.0
    349378212022A Blinded Randomized Trial Comparing Standard Activated Clotting Time Heparin Management to High Target Active Clotting Time and Individualized Hepcon HMS Heparin Management in Cardiopulmonary Bypass Cardiac Surgical Patients.0
    348376012022Impact and predictors of quality of life in adults diagnosed with a genetic muscle disorder: a nationwide population-based study.0
    347848192022Evaluation of an Integrated Smart Sensor System for Real-Time Characterization and Digitalization of Postoperative Abdominal Drain Output: A Pilot Study.0
    346768082022Development and validation of a novel pre-operative comprehensive prognostic score in esophageal squamous cell carcinoma.0
    343893032022Progression to Transplant Under the New Heart Allocation System: The Society of Thoracic Surgeons Intermacs Database.0
    342893082022Direct Cost of Illness for Spinal Cord Injury: A Systematic Review.1
    327622752022Prediction of gestational diabetes mellitus in the first 19 weeks of pregnancy using machine learning techniques.3
    357124552022Effectiveness of Response Inhibition Training and Its Long-Term Effects in Healthy Adults: A Systematic Review and Meta-Analysis.0
    357064862022The global burden of sore throat and group A Streptococcus pharyngitis: A systematic review and meta-analysis.0
    357031902022Exosomal circRNA FNDC3B promotes the progression of esophageal squamous cell carcinoma by sponging miR-490-5p and regulating thioredoxin reductase 1 expression.0
    356933472022Analysis of Genetic Association Between ABCA7 Polymorphism and Alzheimer's Disease Risk in the Southern Chinese Population.0
    356850662022Ultrasound elastography in the diagnosis of biliary atresia in pediatric surgery: a systematic review and meta-analysis of diagnostic test.0
    356818822022The Duration of the Trial Influences the Effects of Mineral Deficiency and the Effective Phytase Dose in Broilers' Diets.0
    356816902022Associations between Smoking and Alcohol and Follicular Lymphoma Incidence and Survival: A Family-Based Case-Control Study in Australia.0


    Pubmed IDLast YearTitleAuthors
    27381631989Proposals for the classification of chronic (mature) B and T lymphoid leukaemias. French-American-British (FAB) Cooperative Group.Bennett JM et al
    93694291997Chromosome aberrations in atypical chronic lymphocytic leukemia: a cytogenetic and interphase cytogenetic study.Bigoni R et al
    90672851997Cytogenetic and interphase cytogenetic characterization of atypical chronic lymphocytic leukemia carrying BCL1 translocation.Cuneo A et al
    9116297199711q deletions identify a new subset of B-cell chronic lymphocytic leukemia characterized by extensive nodal involvement and inferior prognosis.Döhner H et al
    86097311995Cytogenetic analysis of B cell chronic lymphoid leukemias classified according to morphologic and immunophenotypic (FAB) criteria.Hernandez JM et al
    22019151990Prognostic subgroups in B-cell chronic lymphocytic leukemia defined by specific chromosomal abnormalities.Juliusson G et al
    104777111999Mutational status of Ig V(H) genes provides clinically valuable information in B-cell chronic lymphocytic leukemia.Naylor M et al
    100239471999Inactivation of ataxia telangiectasia mutated gene in B-cell chronic lymphocytic leukaemia.Stankovic T et al



  • A classification of chronic (mature) B-cell lymphoproliferative disorders based on reproducible morphologic and immunologic criteria was proposed by the FAB group in 1989. Ever since a number of cytogenetic studies disclosed a remarkable degree of heterogeneity within each disease category. Herein, the main cytogenetic entities of chronic lymphocytic leukemia and related disorders, B-cell prolymphocytic leukemia, splenic lymphoma with villous lymphocytes are presented.
  • Other disease subsets of B-cell CLD include the leukemic phase of follicle centre cell lymphoma, mantle cell lymphoma and lymphoplasmacytic lymphoma. The cytogenetic features of these forms of leukemic lymphoma are the described in the B-NHL classification
  • Comment: The incidence for each of these chromosome lesions (below) is higher when investigated by the more sensitive fluorescence in situ hybridization (FISH) technique: FISH detected 13q14 deletions in 40-50% of the cases, +12 in 15-20% of the cases; 11q22-23 deletions in 7-10% of the cases; 17p13 deletions in 15-20% of the cases. The prognostic significance for each of these anomalies, 11q- excluded, mainly derives from studies that used conventional cytogenetics and needs to be reassessed in the light of the more recent data provided by FISH analysis.
  • Legend for immunophenotypes (below): +: positive in >90% of the cases; +/-: positive in more than 50% of the cases; -/+: positive in less than 50% of cases; -: positive in <10% of the cases; pan-B markers include CD19; CD20; CD79a R = rearranged; sIg: surface immunoglobulins; cyIg: cytoplasmic Ig; IgV genes: genes encoding for the variable portion of the Ig. MTC and mTC1: major translocation cluster and minor translocation cluster 1 of BCL1 region, respectively.
  • Citation

    Antonio Cuneo

    Classification of B-cell chronic lymphoproliferative disorders (CLD)

    Atlas Genet Cytogenet Oncol Haematol. 2000-02-01

    Online version:

    External Links