Biomedical subjects
Publications and source records attributed to I Jinnai.
A simple culture technique for the study of cells from myeloid leukemias and other blood disorders of myeloid series is described. The procedure is the same with that of the ordinary cultures, except for the addition of colony stimulating factor. A large number of mitotic cells can be obtained, and they are quite suitable for banding treatments. Clear banding patterns are consistently obtained.
Various morphological dysplastic changes were observed in patients with chronic myelogenous leukemia, especially in the acute crisis. To clarify their significance, we divided 45 patients in the acute crisis into two groups by our scoring system, the dysplastic group and the non-dysplastic group. Five of 25 subjects in the non-dysplastic group entered complete remission. None of 20 subjects in the dysplastic group did so, and the mean survival after the onset of acute crisis is significantly shorter in the dysplastic group than in the non-dysplastic group. Some patients in the dysplastic group had obvious dysplastic changes several months before the acute crisis. These findings suggest that acute crises in some cases may occur with or be preceded by the development of dysplastic clones similar to myelodysplastic syndrome; these patients respond poorly to conventional chemotherapy.
A 27-yr-old man developed blastic crisis after the chronic phase of Philadelphia chromosome positive chronic myeloid leukemia (CML). The blast cells expressed terminal deoxynucleotidyl transferase (TdT)+/common acute lymphoblastic leukemia antigen (CALLA)+ phenotypes, corresponding to common ALL type. A vincristine plus prednisolone regimen initially suppressed the blastic proliferation, but the blasts soon reappeared as lymphoblasts, and 65% of them possessed basophil-like granules. Immunologic markers were not altered. The blasts were negative for myeloperoxidase, Sudan black B and periodic acid-Schiff reactions, but were positive for toluidine blue (TB) stain and supravital peroxidase (PO) stain using diaminobenzidine (DAB). These blasts were considered to have immature basophil granules. The supravital staining, for TB or PO in combination with fluorescinated-CALLA staining, directly revealed that single blasts expressed both basophil and lymphoid markers. This biphenotypic blast population was found to be a distinct clone from the initial crisis clone by cytogenetic examination. These findings suggest that the CML clone is derived from a multipotent stem cell common to lymphoid and myeloid lineages, or that dual markers may be expressed on transformed lymphoid or basophil clone as the result of differentiation infidelity probably determined by the genetic derangement in acute crisis.
We used a micromethod for cytogenetic analysis from single haematopoietic colonies to study two adults with chronic myelomonocytic leukaemia (CMML) and a boy with juvenile chronic myeloid leukaemia (JCML) carrying distinct chromosome abnormalities, 7q-, der(21), and trisomy 21. We wanted to know if both granulocyte-macrophage (GM) and erythroid precursors are involved in the abnormal clone. In all three patients, their chromosome abnormality was seen in almost all metaphases obtained from GM-colonies and erythroid bursts. Peripheral blood leucocytes stimulated with phytohaemagglutinin exhibited only normal karyotypes. Clones of B-cell produced by Epstein-Barr virus had only normal karyotypes in the CMML patients. These findings indicate that CMML and JCML are clonal haemopathies that originate in a partially committed myeloid progenitor cell.
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Twenty-three adult patients in complete remission (CR) from acute leukemia were investigated for the steady-state bone marrow (BM) CFU-C concentration and the cytochemical findings of neutrophils and monocytes. There was considerable variation in CFU-C concentrations among patients. Patients with abnormality high or low values tended to relapse earlier. Repeated assays revealed constant CFU-C values in individual long-term cases of remission (4 cases). One case of M4 (myelomonocytic) and the case of M5b (monocytic) leukemia revealed a complete lack of nonspecific esterase activity in CR monocytes as well as initial leukemic promonocytes; they also showed abnormally high or low concentrations of CFU-C and relapsed early. This finding suggests that hematopoiesis in CR bone marrow occurs from abnormal stem cells common to initial, acute leukemic clones in such cases.
To investigate the biological differences between adult and childhood acute lymphoblastic leukemia (ALL), leukemic blasts from 33 patients with ALL (22 adults and 11 children) and from 11 patients in the lymphoid crisis of chronic myeloid leukemia (CML) were studied using cytochemical and immunological markers and also by the outcome of their treatment. The cytochemical studies showed that blasts from seven of the adult ALL patients were dense-granular-positive (DG-positive) for beta-glucuronidase, whereas the blasts from the children were negative except for one (with T-ALL). In the adults with common ALL (cALL), survival of patients DG-positive for this enzyme were significantly shorter than that of eight patients with a scattered granular pattern (p less than 0.05). The mean ratio between the percentage of blasts positive for cALL antigen (cALLA) to that of blasts positive for terminal deoxynucleotidyl transferase (TdT) in the adult group with cALL (0.6 +/- 0.3) was significantly lower (p less than 0.01) than in the group of children with cALL (1.1 +/- 0.2) or in the lymphoid-crisis group (1.5 +/- 1.0). These findings indicate that adult cALL consists of two distinct subpopulations, one with less differentiated phenotype (cALL-/TdT+) and the other with more (cALL+/TdT+). In contrast, the blast cells in childhood cALL and some patients in lymphoid crisis had a relatively homogeneous population with the latter phenotypes. The results suggest that the clonotypic cells in adult ALL, particularly in cALL, appear to be more immature than those in childhood ALL. The beta-glucuronidase patterns indicate a further heterogeneity in adult ALL.
A case of Philadelphia (Ph1) chromosome negative chronic myeloid leukaemia (CML) developed lymphoid crisis. Immunological marker studies disclosed that the lymphoid cells were sheep erythrocyte-rosetting-, Leu-1+, Leu-5+, OKT-4+, OKT-8+, common ALL antigen-, HLA-DR-, cytoplasmic and surface immunoglobulin-, MAS 036C(antithymocyte)+ (after in vitro culture) and terminal deoxynucleotidyl transferase-, indicating T-cell phenotypes, probably of common thymocytes. Cytochemical staining also demonstrated immature T-cell characters: dot-positivity for acid phosphatase and beta-glucuronidase, and negative for acid alpha-naphthyl acetate esterase. All bone marrow metaphases exhibited normal karyotypes. Our observation suggests that the neoplastic features of a common stem cell for myeloid and lymphoid cell lines are very similar in Ph1 positive and negative CMLs, and that the stem cell can differentiate towards T-lineage.
Cytochemical investigation of leukemic promyelocytes from 25 cases of acute promyelocytic leukemia (M3) disclosed two major cellular differentiation categories: (1) the pure neutrophilic (N) type (16 cases) with strong myeloperoxidase (MPO) and naphthol-ASD chloroacetate esterase (Es-chl), but lacking the monocytic enzyme NaF-sensitive alpha-naphthyl butyrate esterase (Es-b), and (2) the mixed neutrophilic/monocytoid (N/M) type (seven cases) with strong Es-b as well as strong MPO, all cases exhibiting Es-dual (Es-b + Es-chl) positive cells. Two more cases with unusual phenotypes were noted: one with intense lysozyme activity but without Es-b and the other with toluidine blue-methachromasia and negative MPO. Promyelocytes from the control group, consisting of nine cases of t(8;21) M2 AML and ten cases with normal bone marrow, lacked such cytochemical heterogeneity. HL-60, an M3 cell line that can be induced to differentiate toward monocytic lineage in vitro, was almost negative for Es-b in the uninduced condition. Cytogenetically, eight cases of N type and five of N/M type had the t(15;17) abnormality. Thus at least two differentiation patterns were observed in M3 leukemia with fidelity (N type) and infidelity (N/M type) for normal granulocytic differentiation. In this series, there was no statistically significant difference in clinical features (remission rate and survival) between the two types. Our study suggests that the development of M3 leukemia is not exclusively restricted to the neutrophilic pathway, but more heterogeneously related to myelomonocytic differentiation.
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To clarify the relationship between fibroblastoid colony-forming units (CFU-f) and hemopoietic precursor cells, simultaneous assays of CFU-f, CFU-e, BFU-e, and CFU-c from the bone marrow of 10 healthy volunteers were performed. The number of CFU-f correlated positively with CFU-e (r = 0.905, P less than 0.001) and BFU-e (r = 0.842, P less than 0.005), but not with CFU-c (r = 0.530, P greater than 0.1). These findings support the hypothesis that CFU-f is related to erythropoiesis in the steady state of hemopoietic tissue. Further studies of the relationship between CFU-f and erythroid precursor cells in patients with hematological diseases may help clarify their pathophysiology.
T cell subset composition of peripheral blood and bone marrow from 22 patients with aplastic anaemia (AA) was studied by monoclonal antibodies (OKT3, OKT4 and OKT8). In the peripheral blood, OKT3 (pan-T), OKT4 (helper/inducer-T) and OKT8 (suppressor-T) cells varied widely in number. The ratios of OKT4:OKT8 exhibited the same tendency. However, a subgroup of AA with a reduced ratio of lower than 1.0 was present both in cases with or without prior prednisolone therapy. Of the eight patients treated with immunosuppressants, four with reduced ratios responded, whereas the other four with normal or higher ratios did not. The ratios of two of four responders gradually reached the normal level. These results suggest that the reduced OKT4:OKT8 ratio may be related to the cell-mediated immunosuppressive mechanism postulated as a cause of stem cell inhibition in a subgroup of AA, and indicate prospectively the effectiveness of immunosuppressive therapy.
The number of bone marrow granulocyte-macrophage progenitor cells (CFU-C) and fibroblastoid colony-forming units (CFU-F) was significantly smaller in acute leukemia patients. To analyze the mechanism by which CFU-C and CFU-F were reduced, the study on murine myeloid leukemia was carried out. In murine leukemia, bone marrow CFU-C and CFU-F decreased in number in correlation with the proliferation of leukemic cells. Murine leukemic cells suppressed the growth of CFU-C and CFU-F in the mixed culture of leukemic cells and normal murine marrow cells. Furthermore, leukemic cell-conditioned medium inhibited the growth of CFU-F. The results show that murine leukemic cells themselves and/or humoral factors produced by them give inhibitory effects on the growth of not only CFU-C but also CFU-F.
The clonal origin of radiation-induced thymic lymphoma was studied in mice with cellular mosaicism for phosphoglycerate kinase (PGK). Repeated whole-body X-irradiations (4 doses, 1.7 Gy each) with intervals of 7 days resulted in development of thymic lymphomas in the mosaic mice. PGK from all lymphomas gave only a single spot on electrophoresis. The results demonstrate the single cell origin of the thymic lymphoma.
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