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Acute megakaryoblastic leukemia (AMKL, M7)
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Acute megakaryoblastic leukemia (AMKL) is life-threatening leukemia in which malignant megakaryoblasts proliferate abnormally and injure various tissues. Megakaryoblasts are the most immature precursor cells in a platelet-forming lineage; they mature to promegakaryocytes and, ultimately, megakaryocytes which cells shed membrane-enclosed particles, i.e. platelets, into the circulation. Platelets are critical for the normal clotting of blood. While malignant megakaryoblasts usually are the predominant proliferating and tissue-damaging cells, their similarly malignant descendants, promegakaryocytes and megakaryocytes, are variable contributors to the malignancy.
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Immunophenotype:
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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.
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
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Example:
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Above case shows (lymp-green, grans-blue, blast-red, Monocytes- pink) positivity for cCD61, CD34, CD41, CD36, CD9, CD117 and negativity for CD11b, CD19, ,CD4, HLA-DR, CD56, cCD79a, cCD3
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REFERENCE:
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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. PMID 201318
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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. PMID 2790202
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Cytogenetic profile of childhood and adult megakaryoblastic leukemia (M7): a study of the Groupe Français de Cytogénétique Hématologique (GFCH).
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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. PMID 12091356
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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. PMID 12691142
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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. PMID 11431691
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