Ei-ichi Yao

Chromosomal characteristics of chronic and blastic phases of Ph-positive chronic myeloid leukemia

To evaluate the appearance of chromosome changes, in addition to the Philadelphia (Ph) chromosome, as predictive and diagnostic parameters of transformation in chronic myeloid leukemia (CML), such changes were analyzed in the chronic phase (CP) and compared with those of the blastic phase (BP) of CML. The common chromosome changes observed in the CP were loss of a Y (-Y), trisomy 8 (+8), an isochromosome for the long arm of chromosome #17 [i(17q)], a double Ph (+Ph), reciprocal translocations, and partial deletions. In most patients with chromosome changes in addition to the Ph, the percentage of abnormal clones increased steadily during the CP and was accompanied by other chromosome changes shortly before or at the onset of the BP, except for cases with -Y or i(17q) clones. In general, most chromosome changes observed shortly before or at the BP were complex. These facts suggest that complex chromosome changes could be utilized as predictive and diagnostic parameters of blastic transformation in CML.

Significance of chromosome 14 anomaly at band 14Q11 in Japanese patients with adult T-cell leukemia

The chromosomes of leukemic blood cells in eight Japanese patients with acute adult T‐cell leukemia (ATL) were examined by a direct method or short‐term culture method without any mitogens. Six patients showed a chromosome 14 anomaly with a break at band q11–13: inv(14)(q11q32) in two patients, t(11;14)(p13;q13) in one patient, t(14;14)(q11;q32) in addition to del(14)(q11q13) in another, and only del(14)(q11q13) in two patients. Thus, a proximal 14q rearrangement exists in ATL as in other types of T‐cell malignancies. Based on these facts, the pathogenesis of ATL is discussed in reference to the literature.

Lymphoid crisis with T-cell phenotypes in a patient with Philadelphia chromosome negative chronic myeloid leukaemia

Summary 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.

Cytogenetic studies of human T-cell leukemia virus type I carriers : a family study

Recently, the chromosome 14q11 anomaly has been reported to be specific to adult T-cell leukemia (ATL), and this anomaly has also been confirmed in the preleukemic state of adult T-cell leukemia (pre-ATL) patients. Because the cytogenetic abnormality at the stage of human T-cell leukemia virus type I (HTLV-I) carrier remains uncertain, we performed cytogenetic studies of lymphocytes stimulated with phytohemagglutinin in three HTLV-I carriers and three non-HTLV-I carriers in an ATL family. As a result, in three HTLV-I carriers, four of 311 cells examined (1.3%) had chromosome 14q11 anomaly. However, in three non-HTLV-I carriers, none of 260 cells examined had chromosome 14q11 anomaly. These results suggest that chromosome 14q11 anomaly is already present at the stage of HTLV-I carrier and seems to be an important cytogenetic clue to the pathogenesis of ATL.

16;21 translocation in acute nonlymphocytic leukemia with abnormal eosinophils : a unique subtype

Two patients with acute nonlymphocytic leukemia (ANLL) and t(16;21)(p11;q22) were studied. The patients exhibited such clinical and hematological pictures, characterized by M2 and M4 with eosinophilia (FAB classification), as relatively matured leukemic cells, low neutrophil alkaline phosphatase activity, abnormal eosinophils and a high count of monocytic cells in the bone marrow. The prognosis was poor in both patients. From these data, the chromosomal abnormality of t(16;21)(p11;q22) seems to be specifically associated with a unique subtype of ANLL.

Chromosomal abnormalities in lymphoid crisis of chronic myelogenous leukemia

The karyotypes in six patients with Ph-positive chronic myelogenous leukemia (CML) were investigated during the lymphoid crisis associated with high levels of terminal deoxynucleotidyl transferase (TdT) and/or the common acute lymphoblastic antigen (CALLA). Five of the six patients had only the Ph chromosome, with no other karyotypic abnormalities. The remaining one patient had a hypodiploid karyotype: 44,XY, -1, + der(1;?)(p22;?), -3, -4, -6, -7, -8, -9, +22q-, + mar1, + mar2, + mar3. In four patients with lymphoid crisis expressing TdT and CALLA, the response to treatment with vincristine (VCR) and prednisolone (PRD) was satisfactory, except for the one patient whose karyotype was hypodiploid. A discussion is presented as to whether or not there is a correlation between the karyotypic changes, using banding methods, and TdT expression in patients whose blast cells were categorized morphologically as lymphoblastic at the onset of the blastic phase of CML. Sequential chromosome examinations during the chronic and blastic phases of CML were also performed in this study.

Isochromosome 17q in a case of myelofibrosis with myeloid metaplasia terminating in blastic transformation

A case of myelofibrosis with myeloid metaplasia in a 61-year-old female patient is reported. Cytogenetic studies were performed using short-term culture without phytohemagglutinin. A chromosomal aberration of an isochromosome 17q, [i(17q)], was revealed in 88% of the metaphases of peripheral blood cells in the blastic phase. However, all metaphases of bone marrow cells in the chronic phase showed a normal karyotype. Furthermore, i(17q) was also observed in 10% of the metaphases of spleen cells examined 8 months before blastic transformation. In this case, therefore, the cells with i(17q) were associated with an abnormal clone of blastic transformation, with the abnormal clone originating in the spleen with myeloid metaplasia.

Prognostic significance of the morphological dysplastic changes in chronic myelogenous leukemia

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.

Dual expression of lymphoid/basophil markers on single blast cells transformed from chronic myeloid leukemia.

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.