Shigeo Kariyone

Myeloblastoma with an 8;21 chromosome translocation in acute myeloblastic leukemia.

An 8;21 chromosome translocation was found in cells from myeloblastomas of two acute myeloblastic leukemia (AML) patients. In one patient, a sudden onset of paraplegia, which was caused by an epidural myeloblastoma in the thoracic vertebral canal, was the initial symptom of the disease and that of the first relapse. In the other, myeloblastomas, which occurred in the breasts during a hematologic remission, heralded the first relapse. Karyotypes of tumor cells obtained from both patients showed the t(8;21) and additional chromosome abnormalities. These findings, together with earlier experience and reports in the literature, indicate that myeloblastoma may be unique to the 8;21 translocation, and that certain chromosomal abnormalities additional to the t(8;21) may be necessary for the tumor formation.

Involvement of eosinophils in leukemia: Cytogenetic study of eosinophilic colonies from acute myelogenous leukemia associated with translocation (8;21)

We performed a cytogenetic analysis of eosinophilic colonies grown from bone marrow culture of a patient with acute myelogenous leukemia (FAB-M2) associated with t(8;21). The bone marrow, in which 50.2% myeloblasts and 5.6% eosinophils were observed, gave rise to eosinophilic colonies, as well as colonies consisting of immature myeloid cells. The cytogenetic analyses of the colonies were performed on two occasions. The first study revealed t(8;21) in 15 of 16 metaphases in randomly plucked colonies from a dish, in which 65% of the total colonies were those consisting of immature myeloid cells and 35% were eosinophilic colonies identified by positive staining with Luxol-Fast-Blue. The second study, in which eosinophilic colonies were selectively plucked for cytogenetic analysis, showed Cq- and Gq+ markers, which were considered to be t(8;21), in all metaphases (6/6). Our present study strongly suggests that an involvement of the eosinophilic series in the leukemic process of this patient.

Promyelocytic crisis of chronic myelogenous leukemia without t(15;17)

A case of promyelocytic crisis of chronic myelogenous leukemia is reported. The amount of promyelocytoid blasts in peripheral blood and bone marrow were 70% and 58%, respectively, at the onset of the blastic phase. Cytogenetic analyses during the blastic phase did not reveal t(15;17); however, t(3;21) in addition to the t(9;22) in the karyotype of bone marrow or peripheral blood cells was observed.

Megakaryocytopoiesis in polycythemia vera: characterization by megakaryocytic progenitors (CFU-Meg) in vitro and quantitation of marrow megakaryocytes.

Megakaryocytopoiesis in polycythemia vera (PV) was characterized by in vitro growth of marrow megakaryocytic progenitors (CFU-Meg) and quantitation of megakaryocyte numbers in marrow biopsy specimens in 14 patients with PV. Megakaryocyte numbers and CFU-Meg numbers in the 14 patients were variable, with values from the control range to markedly increased numbers. Nine of the 14 patients showed spontaneous CFU-Meg growth, and the presence or absence of spontaneous CFU-Meg growth was found to be related to the degree of marrow megakaryocyte increase, i.e., those with spontaneous CFU-Meg had higher megakaryocyte numbers. None of the plasmas from the PV patients contained detectable levels of megakaryocyte colony-stimulating activity (Meg-CSA), assayed using the culture with nonadherent normal marrow cells and tested plasma without phytohemagglutinin-stimulated leukocyte-conditioned medium as an exogenous source of Meg-CSA. Increased megakaryocyte numbers and resultant thrombocytosis in PV are likely based on the abnormal population of CFU-Meg.

The significance of cytogenetic findings of erythroid colonies derived from a Ph+ ALL patient: Fundamental differences between Ph+ ALL and blastic phase CML

Cytogenetic analysis was performed on colonies from erythroid burst-forming units (BFU-E) derived from bone marrow (BM) cells of a Ph-positive acute lymphocytic leukemia (Ph+ ALL) patient. A normal diploid karyotype was revealed in all 15 metaphases that could be analyzed in the erythroid colonies. Previous cytogenetic analyses of erythroid colonies obtained from BM cells of patients with Ph+ chronic myelogenous leukemia (CML) revealed that Ph-positive karyotypes were predominant in all 11 cases. Two of them were also examined in blastic phase (BP) and showed 100% Ph+ cells in BFU-E-derived colonies. The present findings suggest that the leukemic process of Ph+ ALL does not involve the erythroid series, which is in contrast to the involvement in CML. This is considered to be a fundamental difference between Ph+ ALL and the blastic phase of CML (BP CML). Clinically, cytogenetic analysis of erythroid colonies from BM cells may constitute a valuable approach for the differential diagnosis between Ph+ ALL and the BP of Ph+ CML.

Detection of platelet consumption in aortic graft with 111In-labeled platelets

Increased platelet consumption in two patients with aortic grafts was detected by scintiphotography using 111In-labeled autologous platelets. There was shortened platelet survival time in these patients. These findings might suggest that platelet consumption in aortic protheses is related to thrombogenesis.

A case of acute myelogenous leukaemia associated with eosinophilia: cytogenetic study of eosinophilic colonies showing the origin of the normal clone

We describe a case of acute myelogenous leukaemia presenting with remarkable eosinophilia in relapse. Since the patient had chromosomal abnormalities, haemopoietic as well as eosinophilic colonies grown in culture were cytogenetically analysed to determine the origin of the eosinophils. Eosinophilic colonies as well as erythroid bursts revealed a normal karyotype, while a short-term culture of peripheral blood cells in relapse revealed an abnormal karyotype which had been observed before treatment. These data clearly demonstrate that the eosinophilia in this case originated from a normal clone. The cytogenetic analysis of eosinophilic colonies is a useful technique for the definite diagnosis of eosinophilic leukaemia or reactive eosinophilia in patients having marker chromosomes.

Characterization of the erythropoietic progenitor cells (BFU-E) in paroxysmal nocturnal haemoglobinuria (PNH)

Summary. In order to investigate erythropoiesis in paroxysmal nocturnal haemoglobinuria (PNH), the relative proportions of complement‐mediated lysed erythroblasts in individual bursts of two cases of PNH were analysed by a modified complement lysis sensitivity test using the trypan blue dye exclusion method. All bursts contained both complement‐sensitive and complement‐insensitive erythroblasts and the ratio between them varied from burst to burst. The means ±SD of the haemolytic percentages of individual bursts in cases 1 and 2 were 30.9 ± 10.8% (n= 20, ranging from 13.2% to 52.8%) and 54.8 ± 16.4% (n= 31, ranging from 26.4% to 82.5%), respectively. In addition, the cumulative frequency distributions of the proportions of complement‐mediated lysed erythroblasts in individual bursts approached normal frequency distributions. These results suggest that two red cell populations with different susceptibilities to complement in PNH are derived from a single population of erythropoietic progenitor cells rather than a dual population of normal and PNH erythropoietic progenitor cells.

ERYTHROPOIESIS OF COMPLEMENT‐SENSITIVE CELLS IN A PNH PATIENT WITH IRON DEFICIENCY ANEMIA DURING IRON THERAPY

Paroxysmal nonturnal hemoglobinuria (PNH) is an acquired disorder characterized by increased susceptibility of erythrocytes (E) to complement (C’)-mediated hemolysis. Although patients with PNH may be treated with androgenic hormones, prednisone and iron, these agents are not always effective. Here we report the changes in the proportion of C’-sensitive E, and the C7 sensitivity of erythroblasts observed by the complement lysis sensitivity (CLS) test and erythropoietic cell culture during iron therapy in a PNH patient with iron deficiency anemia (IDA). Case: A 58-yr-old male was admitted to our hospital because of epistaxis and anemia in June, 1979. Both Ham’s and sugar-water tests were positive, and the patient was diagnosed as having PNH. On 3 June, 1987, laboratory findings showed that the serum iron was 50 pg/dl, total iron binding capacity 440 kg/dl, and serum ferritin 8.6 ng/ml. Therefore, he was diagnosed as having IDA and was treated with sodium ferrous citrate 150 mg/d from July 6, 1987. Iron therapy was continued until September 9, 1987. Slight exacerbation of hemoglobinuria occurred on September 1 and 2, 1987, but it was not necessary to stop the iron therapy (Table 1). Material and methods: The CLS test of E in peripheral blood (PB) and erythroblasts from bursts in bone marrow was performed during the clinical course from June 3, 1987 to September 9, 1987. A modification (1) of the CLS test (2) developed by Rosse & Dacie

Ferrokinetic evaluation of erythropoiesis in patients with myelodysplastic syndromes.

Erythropoietic activity in patients with myelodysplastic syndrome (MDS) was evaluated by ferrokinetic measurements. Since the conventional plasma iron turnover of MDS patients increased with plasma iron levels after multiple blood transfusions, erythron transferrin uptake was chosen as a parameter of erythroid marrow activity. Although a correlation was shown between plasma iron level and plasma iron turnover (r = 0.50, 0.01 less than p less than 0.02), no correlation existed between the plasma iron level and erythron transferrin uptake (r = 0.25, p greater than 0.1). Erythron transferrin uptake, independent of plasma iron, was significantly higher in MDS patients than in normal subjects (110.6 +/- 67.6 and 67.6 +/- 18.8 mumol/l/dl, respectively; 0.01 less than p less than 0.02). An increased erythropoiesis occurring concomitantly with morphologically normal or increased erythroid cellularity was demonstrated in patients with MDS. The measurement of erythron transferrin uptake might be valuable as an accurate expression of erythroid activity in the hyperferremic state.