Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

M3/M3v acute myeloid leukemia (AML M3/M3v)

Acute promyelocytic leukemia (APL)

Written2006-01Claudia Schoch
MLL Münchner Leukümielabor GmbH, Max-Lebsche-Platz 31, 81377 München, Germany

(Note : for Links provided by Atlas : click)


ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9866/3 Acute promyelocytic leukaemia with t(15;17)(q22;q12); PML-RARA
Atlas_Id 1240
Note FAB criteria AML M3 :
  • great majority of cells are abnormal promyelocytes, with a characteristic pattern of heavy granulation
  • characteristic cells contain bundles of Auer rods ("faggots")

    FAB criteria AML M3v

  • minimal granulation, relative scarcity of cells with heavy granulation and cells containing multiple Auer rods. The nucleus of every cell in the peripheral blood is bilobed, multilobed or reniform, but the majority of cells are either devoid of granules or contain only a few fine azurophil granules. However, at least a few cells with all the cytoplasmic features of typical AML M3 are present. If these are overlooked, the cases are likely misdiagnosed as atypical monocytic leukemia. The atypical morphology is mainly a feature of the peripheral blood cells ­ bone marrow morphology is closer to that of typical AML M3.
  • both subtypes show a very strong myeloperoxidase reaction and a negative reaction for non-specific esterase

    Immunophenotype :

  • characteristic but not diagnostic myeloid phenotype
  • CD33 positive, HLA-DR is generally absent
  • in M3 but not M3v: characteristic light scatter pattern, strong unspecific fluorescence signal

    WHO classification

  • distinct entity in category AML with recurrent genetic abnormalities: Acute promyelocytic leukemia (AML with t(15;17)(q24;q21) (PML/RARA) and variants)
  • Clinics and Pathology

    Epidemiology rare: 5 - 8 % of AML, incidence higher in Spain, Italy and Latinos; occurs at any age, predominantly adults in mid-life accounting for aprox. 5% of treatment related leukemias (t-AML)
    Clinics Low WBC in AML M3, high WBC in AML M3v; frequently associated with disseminated intravascular coagulation (DIC) and hyperfibrinolysis
    Cytology The cytomorphology of APL blasts is obviously different in the two subtypes: in AML M3, the abnormal promyelocytes show a heavy granulation and bundles of Auer rods; in AML M3v blasts have a non- or hypogranular cytoplasm or contain fine dustlike cytoplasmic granules that may not be apparent by light microscopy. Furthermore, M3v blasts show a typical bilobed nuclear configuration. This latter morphologic phenotype, together with missing granulation, often resulted in the misleading diagnosis of acute monocytic or myelo-monocytic leukemia before the cytogenetic correlation of both AML M3 and M3v with t(15;17)(q24;q21) was observed. AML M3v accounts for approximately 1/3 of APL cases
    Prognosis Favourable if treated with an ATRA (all trans-retinoic acid) and anthracycline containing regimen: CR in >80% of cases, med survival: in most studies with ATRA treatment not reached yet, adverse prognosis factors: high WBC, FLT3- internal tandem duplication (ITD), bleeding episodes.


    Cytogenetics Morphological t(15;17)(q24;q21) leading to a PML-RARA-rearrangement on the molecular level
    variant translocations involving one ore more chromosomes in addition to 15 and 17 are found in 2-5% of cases with PML-RARA-rearrangement cytogenetically cryptic PML-RARA-rearrangements are observed in 2-3% of APL cases
    Additional anomalies are observed in 35-45% of cases, most frequent: +8, del(9q), ider(17)(q10)t(15;17)
    Variants 3 variant translocation involving RARA: t(11;17)(q23;q12) leading to a fusion of RARA and PLZF; t(5;17)(q23;q12) leading to a fusion of RARA and NPM; t(11;17)(q13;q12) leading to a fusion of RARA and NuMA. The cases with variant translocation have initially been reported as having APL morphology. However, morphological differences exist. Clinically important is that APL variant with t(5;17)(q12;q12) seems to respond to ATRA, while APL variant with t(11;17)(q23;q12) does not.


    A variant form of hypergranular promyelocytic leukaemia (M3)
    Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C
    British journal of haematology. 1980 ; 44 (1) : 169-170.
    PMID 6929699
    WHO histological classification of acute myeloid leukaemias.
    Brunning RD, Matutes E, Harris NL, Flandrin G, Vardiman J, Bennett JM, Head DR
    World Health Organozation of Tumors, Pathology..
    Impact of FLT3 mutations and promyelocytic leukaemia-breakpoint on clinical characteristics and prognosis in acute promyelocytic leukaemia.
    Kuchenbauer F, Schoch C, Kern W, Hiddemann W, Haferlach T, Schnittger S
    British journal of haematology. 2005 ; 130 (2) : 196-202.
    PMID 16029447
    Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia. German AML Cooperative Group.
    Lengfelder E, Reichert A, Schoch C, Haase D, Haferlach T, Löffler H, Staib P, Heyll A, Seifarth W, Saussele S, Fonatsch C, Gassmann W, Ludwig WD, Hochhaus A, Beelen D, Aul C, Sauerland MC, Heinecke A, Hehlmann R, Wörmann B, Hiddemann W, Büchner T
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2000 ; 14 (8) : 1362-1370.
    PMID 10942230
    15/17 translocation, a consistent chromosomal change in acute promyelocytic leukaemia.
    Rowley JD, Golomb HM, Dougherty C
    Lancet. 1977 ; 1 (8010) : 549-550.
    PMID 65649
    Acute myeloid leukemia with recurring chromosome abnormalities as defined by the WHO-classification: incidence of subgroups, additional genetic abnormalities, FAB subtypes and age distribution in an unselected series of 1,897 patients with acute myeloid leukemia.
    Schoch C, Schnittger S, Kern W, Dugas M, Hiddemann W, Haferlach T
    Haematologica. 2003 ; 88 (3) : 351-352.
    PMID 12651278
    All-trans-retinoic acid in acute promyelocytic leukemia.
    Tallman MS, Andersen JW, Schiffer CA, Appelbaum FR, Feusner JH, Ogden A, Shepherd L, Willman C, Bloomfield CD, Rowe JM, Wiernik PH
    The New England journal of medicine. 1997 ; 337 (15) : 1021-1028.
    PMID 9321529


    This paper should be referenced as such :
    Schoch, C
    M3/M3v acute non lymphocytic leukemia (M3-AML) - M3/M3v acute myeloid leukemia (AML M3/M3v) - Acute promyelocytic leukemia (APL)
    Atlas Genet Cytogenet Oncol Haematol. 2006;10(3):184-185.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

    Other genes implicated (Data extracted from papers in the Atlas) [ 26 ]


    External links

    COSMICHisto = - Site = haematopoietic_and_lymphoid_tissue (COSMIC)
    arrayMapTopo ( C42) Morph ( 9861/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
    arrayMapTopo ( C42) Morph ( 9866/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
    Disease databaseM3/M3v acute myeloid leukemia (AML M3/M3v)
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed
    All articlesautomatic search in PubMed

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Tue Mar 14 13:54:04 CET 2017

    Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

    For comments and suggestions or contributions, please contact us