Rokuo Abe

An analysis of chromosome findings in non-Hodgkin's lymphomas

Banding studies were done on tissues from tumors excised from 22 Japanese patients with non-Hodgkins lymphomas. All tumors were found to be associated with aneuploidy. The chromosome abnormalities were diverse, with each chromosome type being involved in these abnormalities. Terminal deletions, derivative chromosomes as a result of unbalanced or nonreciprocal translocations, and markers of totally or partially unknown origin accounted for the majority of the structural abnormalities. Balanced reciprocal translocations were seen only occasionally. The 14q+, 6q-, partial trisomy of 1q, 11q+, 18q+, and 19q+ abnormalities were seen in more than two patients. The incidence of a missing sex chromosome was significantly higher than that of autosomes, but no particular other karyotypic abnormality seemed to be associated with the event. All six patients whose chromosomes could be totally characterized were in complete remission. Patients with one or more markers of unknown either totally or partially origin, had a median survival of only 8 months (p less than 0.01). Five of the former six patients showed a nodular histology. Fifteen of the latter 16 patients had a diffuse histology, with 13 of the 15 having diffuse histiocytic lymphoma. The median survival of 9.5 months for the 14 with only abnormal metaphases in the lymphatic tissues (AA-group) was shorter than the 26+ months for the seven patients with both normal and abnormal metaphases (AN-group). Thus certain aspects of chromosomal changes appear to correlate with histology and/or prognosis in non-Hodgkins lymphomas.

Significance of abnormalities involving chromosomal segment 11q22-25 in acute leukemia

Six hundred and thirty unselected cases of acute leukemia, with complete data regarding age, karyotype (with breakpoints), and the diagnosis according to the FAB classification, were available in the literature and from our unpublished cases for comparing the incidence of chromosomal abnormalities involving the long arm of chromosome #11 among age groups in acute nonlymphocytic leukemia (ANLL) and acute lymphocytic leukemia (ALL). A statistically highly significant difference (p less than 0.001) was observed between the incidence of ANLL cases with chromosome aberrations involving 11q22-25 in childhood (less than or equal to 15 years) versus that in adults (greater than 15 yr). This statistical difference was not only related to infant cases (less than or equal to 12 months), but also to cases of children over 1 year of age. The incidence of the 11q22-25 abnormality in childhood cases (greater than 1 yr to less than or equal to 15 yr) was statistically significant (0.025 less than p less than 0.05) when compared to the incidence in adult cases. The incidence of the 11q22-25 abnormality in infant cases was much higher when compared to that of older cases with either ANLL or ALL (p less than 0.001 in each leukemia). This trend was not observed in cases with the 11q11-21 abnormality and this may imply that the origin and meaning of the 11q11-21 abnormality may differ from that of the 11q22-25 abnormality. Twenty-three infants with acute leukemia (AL) with the 11q22-25 abnormality were available from previous reports and our unpublished case. The median ages of ANLL, ALL, and all AL cases were 16 weeks, 9 weeks, and 15 weeks, respectively. The tendency of the 11q22-25 abnormality to be common in infants with ANLL or ALL under 6 months of age may suggest that it has a close correlation with the origin(s) or mechanism(s) related to the occurrence of infant AL.

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.

Further characterization of acute myelogenous leukemia with t(8; 21) chromosome translocation

Abstract All seven patients with t(8; 21)(q22; q22) and one with a del(8)(q22) had a diagnosis of acute myelogenous leukemia (AML)-M2 type. Similar morphologies of leukemic cells with a t(8q−; 21q+) or with an 8q−, as well as the association of the latter with loss of a sex chromosome, indicated that the translocation or deletion of chromosome No. 8 at q22 may be essential to the phenotypic expression and loss of a sex chromosome in cells with the translocation. Seven patients (one in group I, four in group II, and two in group III) were in remission and four relapsed. All patients at relapse had acquired additional autosomal abnormalities, which were related to changes in cell morphology and relapse.

Chromosomes and causation of human cancer and leukemia. LIV. Near-tetraploidy in acute leukemia

Near-tetraploid cell populations were observed in a case of T-cell acute lymphoblastic leukemia (T-ALL) and in one of acute myeloblastic leukemia (AML). In the ALL case, hyperdiploid chromosomal changes, characterized by an isochromosome 17q [i(17q)], as well as other changes, were seen at the onset of the disease. At the first relapse, hypertetraploid cells appeared in about 10% of the mitoses in the bone marrow (BM), and by the second and third relapses, the hypertetraploidy was present in more than 90% of the mitoses in the BM. Even though karyotypic instability was evident, all abnormal karyotypes contained one or two i(17q) at every sampling. In spite of karyotypic instability at each relapse, karyotypic evolution was observed whenever relapse occurred. A normal female karyotype was confirmed in the BM of each period. Immunologic examinations performed at each sampling revealed no recognizable changes before and after the appearance of tetraploidy. In the AML case, which was classified as FAB M2, cytogenetic examination was performed at diagnosis and relapse. In both, hypotetraploid cells were observed in over 60% of the BM cells; the modal chromosome number was 90. Banding analysis was successful at relapse, and a pseudodiploid clone characterized by t(8;21) and a hypotetraploid clone with two t(8;21) and a loss of two Y chromosomes were observed in the same BM sample. A normal male karyotype was also observed in BM cells. In both cases, giant and bizarre blasts were seen in the BM. A close correlation between near-tetraploid mitoses and giant and bizarre blast cells in BM smears of the same samples was observed. Previously published tetraploid acute leukemia cases analyzed with banding methods were accumulated and compared with our two cases.

North American Burkitt-type ALL with a Variant Translocation t(8;22)

A variant translocation, t(8;22) (q24;q12), was found in bone marrow (BM) and long-term cultured peripheral blood (PB) cells obtained from an American boy with Burkitt-type acute lymphoblastic leukemia (ALL-L3, French-American-British classification). Surface marker studies revealed a monoclonal immunoglobulin A (sIgA) with a lambda chain (74%) on the PB cells in a sample containing 74% blast cells. A table summarizing the cases with variant translocations in Burkitt diseases [Burkitt lymphoma (BL) and ALL-L3] is presented, and review of the published data indicates that, generally, the survival of patients with t(8;22)-type BL and ALL-L3 is short and comparable to that of patients with the more common translocation, t(8;14). There appears to be no relationship between t(2;8) or t(8;22) and a specific heavy-chain sIg. The karyotypes of the BM cells and those of the long-term cultured PB cells, though retaining t(8;22), differed from each other. Chromosomal analyses using cells from long-term culture may reveal karyotypic changes in addition to those seen on direct analysis. The key karyotypic anomaly in Burkitt-type diseases appears to be the breakage of chromosome #8 at band q24.

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.

Burkitt's lymphoma with 2 8 translocation: A aase report with special reference to the clinical features

A case of Japanese Burkitts lymphoma (BL) with a t(2; 8) (p11; q24), a variant translocation in BL, is reported. The patient was a 45-year-old woman in whom a subcutaneous right axillary tumor first occurred. Remission was not achieved despite extensive chemotherapy. Of the four nonendemic BL, two endemic BL, and one nonendemic Burkitt-type acute lymphocytic leukemia (ALL-L3) cases with a t(2; 8) reported so far, including the present case, four (two nonendemic and two endemic) were positive for Epstein-Barr virus-determined nuclear antigen (EBNA) and two revealed extremely high antibody titers against Epstein-Barr virus (EBV), the remaining one not having been tested for EBV. Thus, a possible close relationship between the t(2; 8) and EBV infection has to be considered. The t(2; 8) in nonendemic BL seems to occur more often in adults than in children.

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.