Kanji Sugita

Immunoglobulin heavy chain gene rearrangements and mixed lineage characteristics in acute leukemias with the 11;19 translocation.

Although the origin of acute leukemia with the 4;11 translocation has been shown to be an early myeloid progenitor cell or a stem cell with the potential for differentiation into both lymphoid and myeloid lineage, few precise studies on acute leukemia with the 11;19 translocation have thus far been reported. This study focused on the clinical, morphologic, ultrastructural, and immunologic characteristics as well as the DNA in three cases of acute leukemia with the 11;19 translocation. All three patients were infants and showed hyperleukocytosis. The morphologic feature was French‐American‐British (FAB)‐L2 in two patients, in one of which a few monocytoid blasts were also seen by electron microscopy. Cells from the third patient underwent morphologic changes from FAB‐L2 at the time of diagnosis to M5b at relapse. Immunologic marker studies revealed that the blast cells from all three patients expressed Ia and B4, but none expressed B1, CALLA(J5), T antigens, or SIg. Cells from one patient simultaneously expressed myeloid antigen (MCS‐II) both at diagnosis and relapse. Cells from two patients expressed myeloid antigen after being cultured for a short time in vitro. An analysis of immunoglobulin genes and T‐cell receptor genes revealed rearrangements of the heavy chain genes and germ line configurations of the kappa and lamba light chain genes, and of the T‐cell receptor β chain genes. These findings suggest that acute leukemia with the 11;19 translocation has mixed lineage characteristics as a result of leukemogenesis in a stem cell with the potential for both lymphoid and myeloid, especially monocytic, differentiation.

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

Cytogenetic analyses were performed on 12 adult patients with abnormal megakaryoblastic proliferation which was detected by ultrastructural cytochemical study (platelet peroxidase) and platelet‐megakaryocytesspecific monoclonal antibodies (TP‐80, Plt1, AN51, and KOR‐77). The patients consisted of two patients with myelodysplastic syndromes (MDS), three with acute megakaryoblastic leukemia (AMKL), six with megakaryoblastic transformation in Philadelphia‐positive chronic myelogenous leukemia (CML‐meg‐BC), and one case of chronic myeloproliferative disorder (CMPD). Among them, an inversion of the long arm of chromosome 3 [inv(3)(q21q26)] was found in one AMKL patient with a normal platelet count. Chromosome change at band 3q26 was also found in one MDS patient without thrombocythemia. Furthermore, the long arm of chromosome 13, where rearrangements in myelofibrosis are clustered (13q12→q22) was seen in one MDS patient. Trisomy of chromosome 19 was found in one AMKL patient and three CML‐meg‐BC patients. These findings indicate that cytogenetic abnormalities involving 3q26, 13q, and trisomy 19 are associated with hematologic neoplasia with megakaryocytic lineage in adult patients, although these abnormalities were not related to the survival of the patients. During the period of this study, two acute myelogenous leukemia patients (AML‐M2 and AML‐M5b) with chromosome rearrangements at band 3q21 and thrombocythemia were found, indicating that chromosome abnormality at band 3q21 is related to quantitative platelet dysfunction, whereas that at 3q26 is related to hematologic malignancies with a proliferation of megakaryocytic lineage.

Ph1-positive CML-derived myeloid-monocytoid precursor cell line producing substance(s) that stimulates normal CFU-C

A new Ph1-chromosome positive cell line, KOPM-28. was established from a patient with chronic myelogenous leukemia (CML) in blast crisis. KOPM-28 cells were phenotypically immature: without azurophilic granules; negative for myeloperoxidase and positive for specific and nonspecific esterases. The nonspecific esterase reaction was intensified by TPA, and retinoic acid reinforced the specific esterase reaction without inducing morphological changes. KOPM-28 cells were not phagocytic. The cells expressed complement receptors, myeloid-monocytoid antigens, an Ia-like antigen and T4 antigen. CALLA, T-lymphocyte specific antigens, B-lymphocyte related antigen and platelet-megakaryocyte-megakaryoblast specific antigen were not detected. KOPM-28 cells formed colonies in semi-solid medium; this ability was augmented by GM-CSA. The addition of culture medium conditioned by KOPM-28 cells to normal bone marrow cells resulted in the increase of the CFU-C colonies. These findings indicate that KOPM-28 cells have features of myeloid and monocytoid precursor cells and that they are producing substance(s) which stimulates normal CFU-C.