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M3/M3v acute non lymphocytic leukemia (M3-ANLL)

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

Acute promyelocytic leukemia (APL)

Identity

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)(q22;q12) (PML/RARA) and variants)
    		•

    Clinics and Pathology

    Epidemiology rare: 5 - 8 % of ANLL, 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)(q22;q12) 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

    Cytogenetics Morphological t(15;17)(q22;q12) 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.

    Bibliography

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    Impact of FLT3 mutations and promyelocytic leukaemia-breakpoint on clinical characteristics and prognosis in acute promyelocytic leukaemia.
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    Contributor(s)

    Written01-2006Claudia Schoch
    Labor fĂŒr LeukĂ€mie-Diagnostik, Medizinische Klinik III, Ludwig-Maximilians-UniversitĂ€t - Grosshadern, Marchioninistr. 15, 81377 MĂŒnchen, Germany

    Citation

    This paper should be referenced as such :
    Schoch C . M3/M3v acute non lymphocytic leukemia (M3-ANLL); M3/M3v acute myeloid leukemia (AML M3/M3v); Acute promyelocytic leukemia (APL). Atlas Genet Cytogenet Oncol Haematol. January 2006 .
    URL : http://AtlasGeneticsOncology.org/Anomalies/M3ANLLID1240.html

    This paper is referenced by INIST as such :
    http://documents.irevues.inist.fr/bitstream/2042/38325/1/01-2006-M3ANLLID1240.pdf   [ Bibliographic record ]

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