Acute Megakaryoblastic Leukemia M7

Acute megakaryoblastic leukemia (AMkL) is a rare form of AML. It occurs particularly in infants/children younger than 2 years and in adults older than 50 years and represents 10 percent of childhood AML and 0.5 to 1 percent of adult AML.98,99 AMkL is a heterogeneous disease, comprising at least three entities: M7 with t(1;22)(p13;q13), M7 in Down syndrome (DS), both found in infants and young children, and M7 without DS and without t(1;22), the latter having a typical AML age distribution increasing with age.100

In contrast to other types of AML, bone marrow biopsy is invaluable in helping establish the diagnosis of AMkL. The reason is that in only a few cases does the bone marrow aspirate show more than 30 percent of blast cells. By contrast, the bone marrow biopsy may show many clusters of micromegakary-oblasts. This is associated with an increase in reticulum formation and a corresponding decrease in normal hematopoietic precursors. In the peripheral blood, circulating small blast cells resembling either type I blasts or L2 cells can be found. The morphology of the blast cells reveals cells that are very pleo-morphic; they may vary from very small with dense nuclear chromatin to somewhat larger with a fine reticulated nuclear chromatin and one or three prominent nucleoli. Cytoplasmic blebs or actual platelet shedding may be found surrounding some blasts. Standard cytochemistry can be helpful but is not specific. The blasts are MPO or SBB negative and the ANAE reaction shows distinct localized positivity, compared with the more diffuse staining in monocytes. PAS and ACP reactions can be positive and show a localized pattern reaction. Thus, the diagnosis of AMkL must be confirmed by immunological and electron microscopic cytochemistry studies. According to the EGIL recommendations101 the immunophenotypic characterization of megakaryoblasts relied on the negativity of lymphoid antigens together with either the positivity of two megakary-ocytic markers or the expression of one megakaryocytic marker associated with CD36 positivity. The PPO reaction by electron microscopic cytochemistry has been found to be more sensitive than monoclonal antibodies (mAbs) directed against platelet glycoprotein Ilb/IIIa (CD41) (Plate 14-20).102 However, PPO is also positive in immature erythroblasts. Recent studies have also suggested a close relationship between the erythroid and megakaryocytic lineages since M6 and M7 leukemias expressed mRNAs for alpha-globin, gpllb, erythropoietin receptor, and thrombopoietin receptor but not for MPO.103 These findings support the idea of a common ancestry.104

It should be noted that the diagnosis of AMkL might be difficult when criteria cannot be reached. Myelofibrosis and fibrosis of other organs involved in the malignant process together with the prominent organomegaly have mimicked a solid tumor. In a recent report of 39 cases of AMkL from a t(1;22) study group such misdiagnoses have reached up to 18 percent of cases.105

Marrow fibrosis is one of the characteristics of AMkL.106 Abnormal platelets are postulated to release platelet-derived growth factor (PDGF) from a-granules, in turn stimulating the bone marrow fibroblasts and producing fibrosis. The presence of c-SIS mRNA that encodes a chain of PDGF has been demonstrated in M7 cells.

Prognosis of M7 with DS is good; however, it is worse in M7 with t(1;22) and in other M7 subtypes. Therefore BMT is indicated in those cases except in DS.105

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