Summary
Atypical megakaryoblasts (MKB) or megakaryocytes (MK) are occasionally present in the peripheral blood during the terminal development of chronic myeloid leukemia (CML). We report on a 49-year-old female suffering from Ph1 chromosome-positive CML with typical megakaryoblastic transformation in the peripheral blood and in the bone marrow. The small “blasts” were at the most only slightly larger and were occasionally even smaller than lymphocytes but showed megakaryoblastic or atypical megakaryocytic differentiation. The cytoplasmic cytochemical pattern of the atypical megakaryocytic cells was identical to that of large atypical thrombocytes. Platelet peroxidase was detected upon electron-microscopic (EM) examination. Immunologic characterization disclosed the presence of MK-specific antigens. When cultured in vitro on agar, the blasts transformed spontaneously into large mature MK, exhibiting characteristic cytochemical and immunological patterns. Cytogenetic examination of peripheral blood showed severe abnormalities. The patient did not respond to therapy and died 3 months after manifestation of the blast crisis.
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Bain B, Catovsky D, O'Brien M, Spiers AS, Richards HG (1977) Megakaryoblastic transformation of chronic granulocytic leukemia: an electron microscopy and cytochemical study. J Clin Pathol 30: 235–242
Barka T, Anderson FJ (1962) Histochemical methods for acid phosphatase using hexazonium pararosanilin as a coupler. J Histochem Cytochem 10: 741–748
Breton-Gorius J, Reyes F (1976) Ultrastructure of human bone marrow cell maturation. Int Rev Cytol 46: 252–265
Breton-Gorius J, Reyes F, Vernant JP, Tulliez M, Dreyfus B (1978) The blast crisis of chronic granulocytic leukemia: megakaryoblastic nature of cells as revealed by the presence of platelet peroxidase: a cytochemical ultrastructural study. Br J Haematol 39: 295–303
Castoldi GL, Grusovin GD, Scapoli GL (1975) Consecutive cytochemical staining for the analysis of the blastic population in the acute phase of chronic myeloid leukemia. Biomedicine 23: 12–16
Castro-Malaspina H, Moore MAS (1982) Pathophysiological mechanisms operating in the development of myelofibrosis. Role of megakaryocytes. Nouv Rev Fr Hematol 24: 221–226
Castro-Malaspina H, Rabellino EM, Yen A, Nachman RL, Moore MAS (1981) Human megakaryocyte stimulation of proliferation of bone marrow fibroblasts. Blood 57: 781–787
Den Ottolander GJ, Te Velde J, Brederoo P, Geraedts JPM, Slee PHT, Willemze SR, Zwaan FE, Haak HL, Muller P, Bieger R (1979) Megakaryoblastic leukemia (acute myelofibrosis): a report of three cases. Br J Haematol 42: 9–20
El Mohandes E, Hayhoe FGJ (1983) 5-nucleotidase activity of megakaryoblasts in a case of acute megakaryoblastic leukemia. Br J Haematol 53: 523–526
Fialkow PJ, Denman AM, Jacobson RJ, Lowenthal MN (1978) Chronic myelocytic leukemia: origin of some lymphocytes from leukemic stem cells. J Clin Invest 62: 815–823
Fialkow PJ, Jacobson RJ, Papayannopoulou T (1977) Chronic myelocytic leukemia: clonal origin in a stem cell common to the granulocyte, erythrocyte platelet and monocyte/macrophage. Am J Med 63: 125–129
Flandrin G, Daniel MT, Valensi F, Schaison G, Breton-Gorius J (1977) Leucémie aigue à megacaryoblastes. Etude clinique et morphologique de 11 observations. Actual Hematol 11: 200–214
Franzen S, Strenger G, Zajicek J (1981) Mikroplanimetric studies on megakaryocytes in chronic granulocytic leukemia and polycythemia vera. Acta Haematol 26: 182–189
Geissler D, Konwalinka G, Peschel C, Boyd J, Odavic R, Braunsteiner H (1983) Clonal growth of human megakaryocytic progenitor cells in a micro-agar culture system: Simultaneous proliferation of megakaryocytic, granulocytic and erythroid progenitor cells (CFU-M, CFU-C, BFU-E) and T-lymphocytic colonies (CFU-TL). Intern J Cell Clon 1: 377–388
Hayhoe FGJ, Quaglino D (1980) Haematological Cytochemistry. Churchill Livingstone, Edinburgh
Hemmler G (1948) Leucémie mégacaryocytaire avec thrombocythémie. J Suisse Med 78: 976–981
Hossfeld DK, Tormey D, Ellison RR (1975) Ph'-positive megakaryoblastic leukemia. Cancer 36: 576–581
Huhn D, Ascher S (1975) Mikrokaryoblastenschub bei chronischer Myelose. Acta Haematol 53: 183–190
Jacobson RJ, Salo A, Fialkow PJ (1978) Agnogenic myeloid metaplasia: a clonal proliferation of hematopoietic stem cells with secondary myelofibrosis. Blood 51: 189–194
Kaplow LS (1955) A histochemical procedure for localizing and evaluating leukocyte alkaline phosphatase activity of blood and bone marrow. Blood 10: 1023–1034
Lorbacher P, Yam LT, Mitus WJ (1967) Cytochemical demonstration of β-glucuronidase activity in blood and bone marrow cells. J Histochem Cytochem 15: 680–688
Mähr, G, Rindler R, Schmalzl F (1973) Zur Spezifität des Glykogennachweises in Leukozyten, Leber und quergestreiftem Muskel. Glykogenhydrolyse durch alpha-1,6-Amylo-glukosidase. Klin Wochenschr 51: 570–580
Marie JP, Vernant JP, Dreyfus B, Breton-Gorius J (1979) Ultrastructural localisation of peroxidases in undifferentiated blasts during the blast crisis of chronic granulocytic leukemia. Br J Haematol 43: 549–558
Marchal G, Duhamel G (1954) La leucémie à megacaryocytes (à propos de 5 observations). Sem Hop Paris 15: 887–892
Mazur EM, Hoffman R, Chasis J, Marchesi S, Bruno E (1981) Immunofluorescent identification of human megakaryocyte colonies using an anti-platelet glycoprotein anti-serum. Blood 57: 277–288
Mehta AB, Baughan AS, Catovsky D, Goldmann JM, Johnson SA, Galton DAG (1983) Reversal of marrow fibrosis in acute megakaryoblastic leukemia after remission-induction and consolidation chemotherapy followed by bone marrow transplantation. Bri J Haematol 53: 445–450
Minot GR (1922) Megakaryocytes in the peripheral circulation. J Exp Med 36: 1–12
Moloney WC, McPherson K, Fliegelman L (1960) Esterase activity in leukocytes demonstrated by the use of naphthol-AS-D-chloroacetate substrate. J Histochem Cytochem 8: 200–207
Ogawa M, Fried J, Sakai Y, Strife A, Clarkson BD (1970) Studies of cellular proliferation in human leukemia. VI. The proliverative activity, generation time, and emergence time of neutrophilic granulocytes in chronic granulocytic leukemia. Cancer 25: 1031–1049
Olah E, Rak K (1981) Prognostic value of chromosomal findings in the blast phase of Ph'-positive chronic myeloid leukmia. Cancer 27: 287–295
Peterson LC, Bloomfeld CD, Brunning RD (1976) Blast crisis as an initial or terminal manifestation of chronic myeloid leukemia. A study of 28 patients. Am J Med 60: 209–220
Prigogina EL, Fleischman EW, Volkowa MA, Frenkel MA (1978) Chromosome abnormalities and clinical and morphological manifestations of chronic myeloid leukemia. Hum Genet 41: 143–156
Rabellino EM, Nachman RL, Williams N, Winchester RJ, Ross GD (1979) Human megakaryocytes. I. Characterization of the membrane and cytoplasmic components of isolated marrow megakaryocytes. J Exp Med 147: 1273–1281
Rabellino EM, Levene RB, Leung LLK, Nachman RL (1981) Human megakaryocytes. II. Expression of platelet proteins in early marrow megakaryocytes. J Exp Med 154: 88–95
Rosenthal S, Canellos GP, DeVita VT, Gralnick HR (1977) Characteristics of blast crisis in chronic granulocytic leukemia. Blood 49: 705–714
Schaefer HE, Fischer R (1968) Der Peroxidasenachweis an Ausstrichpräparaten sowie an Gewebsschnitten nach Entkalkung Paraffineinbettung. Klin Wochenschr 46: 1228–1235
Schmalzl F, Braunsteiner H (1968) Cytochemische Darstellung von Esteraseaktivitäten in Blut- und Knochenmarkszellen. Klin Wochenschr 46: 642–653
Sonta S, Sandberg AA (1978) Chromosomes and causation of human cancer and leukemia. XXIX. Further studies an karyotypic progression in CML. Cancer 41: 153–164
Tabilio A, Vainchenker W, Van Haecke D, Vinci G, Deschamps JF, Guichard J, Henri A, Xu FS, Reyes F, Breton-Gorius J (1984) Immunological characterization of the leukemic megakaryocytic line at light and electron microscopic levels. Leuk Res 8: 769–781
Though IM, Jacobs PA, Court Brown WM, Beikei AG, Williamson ERD (1963) Cytogenetic studies on bone marrow in chronic myeloid leukemia. Lancet 1: 844–846
Undritz E, Nusselt-Bohaumilitzky K (1968) Über das Auftreten diploider Megakaryoblasten, Promegakaryozyten und Megakaryozyten bei schweren Hämopathien: ein Rückgriff in die Phylogenese. Schweiz Med Wochenschr 98: 1686–1687
Vainchenker W, Deschamps JF, Bastin JM, Guichard J, Titeux M, Breton-Gorius J, McMichael A (1982) Two monoclonal antiplatelet antibodies as markers of human megakaryocyte maturation: immunofluorescent staining and platelet peroxidase detection in megakaryocytic colonies and in vivo cells from normal and leukemic patients. Blood 59: 514–522
Whang-Peng J, Canellos GP, Carbone PP, Tjio JH (1968) Clinical implication of cytogenetic variants in chronic myeloid leukemia (CML). Blood 32: 755–766
Williams WC, Weiss GB (1982) Megakaryoblastic transformation of chronic myelogenous leukemia. Cancer 49: 921–926
Yam LT, Li CY, Crosby WH (1971) Cytochemical identification of monocytes and granulocytes. Am J Clin Pathol 55: 283–290
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Lingg, G., Schmalzl, F., Breton-Gorius, J. et al. Megakaryoblastic micromegakaryocytic crisis in chronic myeloid leukemia. Blut 51, 275–285 (1985). https://doi.org/10.1007/BF00320522
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DOI: https://doi.org/10.1007/BF00320522