|Written||2003-11||Antonio Cuneo, Francesco Cavazzini, Gianluigi Castoldi|
|Hematology Section, Dept. Of Biomedical Sciences, University of Ferrara, 44100 Ferrara Italy|
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|ICD-Topo||C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS|
|ICD-Morpho||9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS|
|ICD-Morpho||9910/3 Acute megakaryoblastic leukaemia|
|Note||Sometimes presenting as "acute myelofibrosis"|
2. Clinics and Pathology
|Phenotype / cell stem origin|| This leukemia is thought to derive from the transformation of a multipotent myeloid progenitor cell. In the adult patient multilineage dysplasia is a common finding and in some cases a minority of myeloid blast cells is present.|
The blast cells show one or more megakaryocytic markers (i.e. Factor VIII, CD61, CD41, or CD42), they test negative when using the anti-myeloperoxidase monoclonal antibody and never show coordinated expression of lymphoid markers, though isolated CD2 or CD7 positivity can be found on some occasions. The CD34, CD13 and CD33 markers are positive in a substantial fraction of cases, as is the case with the CD36/thrombospondin receptor.
The myeloperoxidase stain is negative by light microscopy, but ultrastructural peroxidase activity with a specific peri-nuclear staining pattern can be detected at the electron microscopy level.
|Epidemiology||The disease is rare and, due to difficulty in diagnosis, its exact incidence is not known. Reasonably, it may account for approximately 1-2% of all de novo acute myeloid leukemias (AML) in the adult population, but the incidence in the pediatric age group is higher, partly due to an association with Down syndrome.|
|Clinics|| The presentation is usually acute, though AMegL may develop after myelodysplastic syndrome or chronic myelogenous leukemia (CML).|
In some cases acute myelofibrosis is the presentation picture.
AMegL should be distinguished from AML with megakaryoblastic involvement showing a minority of megakaryoblasts.
In children there is an association with Down syndrome.
|Cytology||The blast cell morphology varies from case to case. In some patients the blasts are undifferentiated and the diagnosis requires immunophenotyping or electron microscopy studies. Dysmegakaryocytopoiesis is rather frequent. Other patients may show bleb-forming blasts, but this feature is nor specific for megakaryoblasts. Micromegakaryocytes can be frequently seen.|
|Pathology|| The bone biopsy almost invariably shows fibrosis, which can be extensive in up to 75% of the cases.|
Spleen enlargement is frequently seen in children, less frequently in adults.
|Treatment||Myeloablative treatment followed, whenever possible, by allogeneic or autologous bone marrow transplant is the treatment of choice|
|Prognosis||In general, the prognosis is severe. 30-to-50 % of the adult patients achieve a complete morphologic remission, but the majority relapse within a few months. Median duration of CR and survival in a study was 10.6 months and 10.4 months, respectively. Some children may fare better, with a 50% 3-year event free survival in AML-M7 post Down Syndrome or with the t(1;22) (see below). Prognosis is dismal in children with other cytogenetic abnormalities.|
|Cytogenetics Morphological|| a) Adults|
There is no cytogenetic anomaly that is specific for AML-M7. The karyotype is abnormal in the vast majority of cases with complex aberrations (i.e. 3 or more clonal aberrations) occurring more frequently than in other AMLs. -5/5q- and/or -7/7q+ are found, as a rule, in virtually all cases with complex karyotype, which globally account for 70-80% of abnormal cases.
3q21 or q26 aberrations are found in 20-30% of the cases; the t(9;22) is another recurrent chromosome aberrations in de novo AML-M7.
Trisomy 19 and 21 may occur in de novo as well as in secondary AML-M7. They are the most frequently occurring chromosome gains and they may be associated with any of the cytogenetic group listed above.
|Cytogenetics Molecular|| Partial trisomy 19, involving the q13 band, can be shown to occur at a 20-30% incidence by comparative genomic hybridization |
The t(1;22)(p13;q13) fuses the OTT(RBM15) gene on 1p13 to the MAL(MLK1) gene on chromosome 22, leading to the OTT-MAL fusion gene on the derivative 22
4. Genes involved and Proteins
|Gene Name||RBM15 (RNA binding motif protein 15)|
|Gene Name||MKL1 (megakaryoblastic leukemia (translocation) 1)|
5. Result of the chromosomal anomaly
|Note||The fusion gene OTT-MAL is on the der(22) chromosome and contains almost all of the sequences of each gene.|
|Frequent gain of chromosome 19 in megakaryoblastic leukemias detected by comparative genomic hybridization.|
|Alvarez S, MacGrogan D, Calasanz MJ, Nimer SD, Jhanwar SC|
|Genes, chromosomes & cancer. 2001 ; 32 (3) : 285-293.|
|Megakaryoblastic acute leukemia: identification by the ultrastructural demonstration of platelet peroxidase.|
|Breton-Gorius J, Reyes F, Duhamel G, Najman A, Gorin NC|
|Blood. 1978 ; 51 (1) : 45-60.|
|Multipotent stem cell involvement in megakaryoblastic leukemia: cytologic and cytogenetic evidence in 15 patients.|
|Cuneo A, Mecucci C, Kerim S, Vandenberghe E, Dal Cin P, Van Orshoven A, Rodhain J, Bosly A, Michaux JL, Martiat P|
|Blood. 1989 ; 74 (5) : 1781-1790.|
|Cytogenetic profile of childhood and adult megakaryoblastic leukemia (M7): a study of the Groupe Français de Cytogénétique Hématologique (GFCH).|
|Dastugue N, Lafage-Pochitaloff M, Pagès MP, Radford I, Bastard C, Talmant P, Mozziconacci MJ, Léonard C, Bilhou-Nabéra C, Cabrol C, Capodano AM, Cornillet-Lefebvre P, Lessard M, Mugneret F, Pérot C, Taviaux S, Fenneteaux O, Duchayne E, Groupe Français d'Hematologie Cellulaire, Berger R|
|Blood. 2002 ; 100 (2) : 618-626.|
|Acute megakaryoblastic leukaemia: a national clinical and biological study of 53 adult and childhood cases by the Groupe Français d'Hématologie Cellulaire (GFHC).|
|Duchayne E, Fenneteau O, Pages MP, Sainty D, Arnoulet C, Dastugue N, Garand R, Groupe Français d'Hématologie Cellulaire, Groupe Français de Cytogénétique Hématologique (GFCH)., Flandrin G|
|Leukemia & lymphoma. 2003 ; 44 (1) : 49-58.|
|Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia.|
|Ma Z, Morris SW, Valentine V, Li M, Herbrick JA, Cui X, Bouman D, Li Y, Mehta PK, Nizetic D, Kaneko Y, Chan GC, Chan LC, Squire J, Scherer SW, Hitzler JK|
|Nature genetics. 2001 ; 28 (3) : 220-221.|
|Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia.|
|Mercher T, Coniat MB, Monni R, Mauchauffe M, Nguyen Khac F, Gressin L, Mugneret F, Leblanc T, Dastugue N, Berger R, Bernard OA|
|Proceedings of the National Academy of Sciences of the United States of America. 2001 ; 98 (10) : 5776-5779.|
|Chromosome 19 abnormalities are commonly seen in AML, M7.|
|Nimer SD, MacGrogan D, Jhanwar S, Alvarez S|
|Blood. 2002 ; 100 (10) : 3838-3839.|
|Leukemias with megakaryoblastic involvement: clinical, hematologic, and immunologic characteristics.|
|San Miguel JF, Gonzalez M, Cañizo MC, Ojeda E, Orfao A, Caballero MD, Moro MJ, Fisac P, Lopez Borrasca A|
|Blood. 1988 ; 72 (2) : 402-407.|
|Acute megakaryocytic leukemia: the Eastern Cooperative Oncology Group experience.|
|Tallman MS, Neuberg D, Bennett JM, Francois CJ, Paietta E, Wiernik PH, Dewald G, Cassileth PA, Oken MM, Rowe JM|
|Blood. 2000 ; 96 (7) : 2405-2411.|
|Megakaryoblastic leukemia and Down's syndrome: a review.|
|Zipursky A, Peeters M, Poon A|
|Pediatric hematology and oncology. 1987 ; 4 (3) : 211-230.|
|This paper should be referenced as such :|
|Cuneo, A ; Cavazzini, F ; Castoldi, GL|
|Acute megakaryoblastic leukemia (AMegL) - M7 acute non lymphocytic leukemia (M7-AML)|
|Atlas Genet Cytogenet Oncol Haematol. 2004;8(1):29-30.|
|Free journal version : [ pdf ] [ DOI ]|
|On line version : http://atlasgeneticsoncology.usal.es/classic/Anomalies/M7ANLLID1100.html|
8. External links
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|© Atlas of Genetics and Cytogenetics in Oncology and Haematology||indexed on : Wed Nov 28 16:17:21 CET 2018|
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