Acute leukemia with megakaryocytic differentiation: a study of 12 cases identified immunocytochemically

Abstract

Acute leukemia with megakaryocytic differentiation has been an uncommonly recognized disorder. We used specific monoclonal and polyclonal antibody reagents (HP1–1D antibody and anti-factor VIII antibody, respectively) and an immunocytochemical staining technique to identify the megakaryocytic nature of the leukemic cells of 12 patients who presented with acute leukemia. The leukemic cells of our patients demonstrated the presence of one or both of these platelet- and megakaryocyte-related antigens, but were negative for all of the commonly employed cytochemical and immunocytochemical staining reactions, except for diffuse acid phosphatase activity and granular PAS positivity. Morphologically, the leukemic cells varied in size from 10 to 40 microns in diameter, frequently had cytoplasmic budding, and contained occasional vacuoles and/or peroxidase-negative azurophilic granules. Five patients presented with syndromes of acute myelofibrosis, and seven patients had otherwise unclassifiable acute leukemias, including three patients who had secondary leukemias. Diffuse reticulin myelofibrosis was present in all cases in which it was sought. Chromosomal abnormalities of leukemic cells were found in five cases. Two patients had deficiencies of plasma coagulation factor V. Study of one patient revealed significant platelet dysfunction. When cytoreductive chemotherapy of leukemia was attempted, the observed response was generally poor, with the exceptions of one patient who has remained in complete remission following treatment with etoposide (VP- 16) and a second patient who attained remission following bone marrow transplantation. These cases of acute megakaryoblastic leukemia represented from 3.6% to 9.3% of all acute leukemia cases diagnosed concomitantly in our institution. Acute leukemia with megakaryocytic differentiation may occur more frequently than previously recognized, may present with differing syndromic features, and can be identified by the use of specific antibody reagents and relatively simple immunocytochemical techniques.

A prospective trial of the treatment of acute megakaryoblastic leukaemia

“…Megakaryoblastic leukaemia is a myeloid malignancy whose prevalence has been previously underestimated: in some countries 8-10% of all cases of acute leukaemia are M-7 leukaemias (Bloomfield & Brunning 1985;Huang et al 1984;Ruiz-Argiielles et al 1986). The morphological features of the malignant cells have been described by the FAB group (Bennet et al 1985), but it seems that morphology alone has a limited value in the identification of the malignancy, hence immunological or electron microscopy features are required to define precisely M-7 acute leukaemias.…”

“…Since the first description of a leukaemia of megakaryoblasts by von Boros & Korenyi (1931), isolated cases or small series of this malignancy have been described (Breton-Gorius et al 1978;Devan, Rose & Greaves 1982;Huang et al 1984;Ruiz-Argiielles et al 1986). Recently, the French-American-British Cooperative Group (FAB) has proposed this type of leukaemia as the M-7 variant (Bennet et al 1985); it seems clear that in most cases of M-7 leukaemia, its identification can not be accomplished solely by the morphology of the blast cells (Bloomfield & Brunning 1985;Huang et al 1984;Ruiz-Argiielles et al 1986). The usefulness of monoclonal antibodies to thrombocytic-lineage specific antigens in the identification of M-7 leukaemias has now been proved (Huang et al 1984;Ruiz-Argiielles et al 1986).…”

“…Recently, the French-American-British Cooperative Group (FAB) has proposed this type of leukaemia as the M-7 variant (Bennet et al 1985); it seems clear that in most cases of M-7 leukaemia, its identification can not be accomplished solely by the morphology of the blast cells (Bloomfield & Brunning 1985;Huang et al 1984;Ruiz-Argiielles et al 1986). The usefulness of monoclonal antibodies to thrombocytic-lineage specific antigens in the identification of M-7 leukaemias has now been proved (Huang et al 1984;Ruiz-Argiielles et al 1986). We have previously published our experience in the identification of M-7 leukaemias in Mexico (Ruiz-Argiielles et al 1986), with very similar findings to those obtained at the Mayo Clinic in the United States (Huang et al 1984).…”

“…The usefulness of monoclonal antibodies to thrombocytic-lineage specific antigens in the identification of M-7 leukaemias has now been proved (Huang et al 1984;Ruiz-Argiielles et al 1986). We have previously published our experience in the identification of M-7 leukaemias in Mexico (Ruiz-Argiielles et al 1986), with very similar findings to those obtained at the Mayo Clinic in the United States (Huang et al 1984). One particular finding that caught our attention was the frequency with which M-7 leukaemias resemble lymphoblastic leukaemias, mainly the L-2 variant (Ruiz-Argiielles et al 1986).…”

Cytogenetic findings in adult acute leukemia and myeloproliferative disorders with an involvement of megakaryocyte lineage

“…It has been postulated that cytogenetic changes in the long arm of chromosome 3 (3q) play a role in various hematologic malignancies such as thrombocythemia and dysmegakaryo~ytopoiesis.~-'~ However, Mecucci et al doubted this association and further speculated that some patients with 3q abnormalities might be diagnosed as having AM=. *' In fact, some patients with AMKL were shown to manifest abnormalities at 3q, i.e., inv(3) (q21q26)'5,'9 or del(3) (q21q26),2' and megakaryoblastic proliferation has also been associated with hematologic neoplasia, such as myelodysplastic syndromes2* and blastic crisis in chronic myeloproliferative disorder^.^,*,^^ However, it is unknown whether patients with abnormal megakaryoblastic proliferation manifest specific karyotypic abnormalities or not, since there are few reports of detailed chromosome studies of patients whose megakaryoblastic proliferation was identified by modern he- No. 4 matologic techniques.…”