Naoki Sadamori

Incidence of intracranial meningiomas in Nagasaki atomic-bomb survivors

Among the Nagasaki atomic‐bomb survivors registered at the Scientific Data Center for Atomic‐Bomb Disaster, Nagasaki University School of Medicine, 45 cases of surgically treated intracranial meningioma were collected from 6 hospitals with departments of neurosurgery in or near Nagasaki City during the period from 1973 to 1992. All 45 patients were over 40 years of age at the time of diagnosis. Subsequently, the 45 cases were statistically analyzed in relationship to the estimated distance from the hypocenter by age, gender, intracranial location, histology and latent period. The analysis showed a high correlation between incidence of meningiomas and distance from the hypocenter. The incidence among Nagasaki atomic‐bomb survivors over 40 years of age, especially in those proximally exposed, appears to be increasing, in inverse proportion to the exposure distance, since 1981, 36 years after the explosion of the atomic bomb.

Frequency of eosinophilia in adult T‐cell leukemia/lymphoma

Cases of adult T‐cell leukemia/lymphoma (ATLL) display several peculiar clinical features, including skin rash, hypercalcemia, and an increase in the absolute neutrophil count. The patients rarely have pronounced eosinophilia. In this study, the eosinophilia observed in lymphoproliferative disorders of 62 patients with ATLL, 27 with T‐cell lymphoma (TL), and 19 with B‐cell lymphoma (BL) was investigated. The incidence of eosinophilia (⩾ 570/μl) was higher in patients with ATLL than in patients with TL or BL. Thirteen patients with ATLL (21.0%), 3 with TL (11.1%), and 2 with BL (10.5%) had eosinophilia. Of these patients, three with ATLL and one with TL who had a pathologic diagnosis of immunoblastic lymphadenopathy (IBL) showed pronounced eosinophilia up to 10,934/μl. Because the number of eosinophils in the peripheral blood of these patients correlated both with the number of ATLL cells and the degree of lymphadenopathy and because this fluctuated with chemotherapy, it seems likely that the secretion of some lymphokines by the lymphoma cells is responsible for the eosinophilia. Cancer 1992; 69:966–971.

Consistent detection of CALM-AF10 chimaeric transcripts in haematological malignancies with t(10;11)(p13;q14) and identification of novel transcripts

The t(10;11)(p13‐14;q14‐21) is a rare but recurring translocation associated with acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Recently the CALM gene was cloned from the t(10;11) breakpoint of U937 and fused to AF10, a putative transcription factor, which had been identified as one of the fusion partners of the MLL gene. In order to define the involvement of these genes in primary leukaemias and cell lines with t(10;11), we analysed the expression of fusion transcripts by reverse transcriptase‐polymerase chain reaction (RT‐PCR) in five patient samples including ALL, AML and lymphoblastic lymphoma, and three monocytic cell lines (P31/Fujioka, KP‐Mo‐TS and U937). The CALM‐AF10 fusion transcript was detected in all samples; however, the AF10‐CALM fusion was not detected in two patient samples and one cell line. In RT‐PCR analysis there were six isoforms of the CALM‐AF10 fusion transcripts and five of AF10‐CALM fusion transcripts. We also detected novel transcripts in U937. Sequence analysis revealed that all these isoforms had in‐frame junctions and that some of them resulted from alternative splicing at different exons of CALM and others from different breakpoints at CALM and/or AF10. There were at least two different breakpoints of CALM and three of AF10 gene. Our results suggest that the CALM‐AF10 fusion gene is a constant feature and is involved in the pathogenesis of haematological malignancies with t(10;11)(p13‐14;q14‐21), showing various and often multilineage phenotypes. Thus, t(10;11) needs to be investigated by RT‐PCR for identification of the genes involved.

Morphological subtyping of acute myeloid leukemia with maturation (AML-M2): homogeneous pink-colored cytoplasm of mature neutrophils is most characteristic of AML-M2 with t(8;21)

Morphologic and cytochemical features of 30 acute myeloid leukemia subtype M2 (AML-M2) patients with t(8;21) were compared with those of 50 AML-M2 patients without t(8;21). It was disclosed that irregular nuclear shape, Auer bodies, and at least 90% myeloperoxidase positivity in blast cells, and pseudo-Pelger-Huët anomaly of the nuclei and homogeneous pink-colored cytoplasm of mature neutrophils were observed in 90–100% of the t(8;21)+ patients. The percentages of patients showing these features were significantly (P < 0.01) lower in the t(8;21)− group. Among these morphological features, homogeneous pink-colored cytoplasm of mature neutrophils is most characteristic of t(8;21)+ AML-M2, because it was seen in 90% of the t(8;21)+ patients but in only 2% of the t(8;21)− patients. Conversely, pale-colored cytoplasm without any granules in mature neutrophils or dyserythropoietic features was observed in 84% of the t(8;21)− patients, but in none of the t(8;21)+ patients. These data suggest that it is possible to subtype AML-M2 patients morphologically by the recognition of homogeneous pink-colored or pale-colored cytoplasm of mature neutrophils and dyserythropoietic features. Thus, the morphologic subtyping of AML-M2 can be utilized alone or in combination with chromosomal or molecular subtyping for biological and clinical studies of AML with maturation.

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.

High Rate of Chromosomal Abnormalities in HTLV-I-Infected T-Cell Colonies Derived from Prodromal Phase of Adult T-Cell Leukemia: A Study of IL-2-Stimulated Colony Formation in Methylcellulose

To detect chromosomal abnormalities in prodromal phase of adult T-cell leukemia (ATL), we established a clonal culture method for human T-lymphotropic virus type I (HTLV-I) infected T-cells in methylcellulose containing recombinant human interleukin 2 (rhIL-2). We tried to analyze chromosomes of 187 colonies (4, 23, 69, 74, and 17, from HTLV-I-uninfected normal T-cells, HTLV-I-Infected normal T-cells, HTLV-I carriers, smoldering ATL, and chronic ATL, respectively), using chromosomal banding methods. In the prodromal group, 53% of colonies (84/160) (36/69, 37/74, 11/17 in HTLV-I carriers, smoldering ATLs, and chronic ATL, respectively) had chromosomal abnormal clones. In HTLV-I carriers, multiple clones with simple chromosomal abnormalities were observed. In more progressed chronic ATL, more complex chromosomal abnormalities were detected, and specific colonies were selected. Thus, colonies in the prodromal phase of ATL are characterized by cytogenetical clonal evolution and clonal changes.

Clinical significance of cytogenetic findings in untreated patients with B-cell chronic lymphocytic leukemia

The chromosome constitutions of stimulated lymphocytes in 21 untreated cases with B-cell chronic lymphocytic leukemia (B-CLL) were examined. So-called polyclonal B-cell activators, i.e., pokeweed mitogen, Epstein-Barr virus, and lipopolysaccharide W from E. coli 055:B5, were used. Four out of 21 cases showed abnormal clones with trisomy 12 and were started on therapy shortly after the diagnosis and cytogenetic examination. On the other hand, most cases without abnormal clones had not received treatment for relatively long periods before and after cytogenetic examination. These findings may indicate that cytogenetic results can be utilized as a parameter for treatment and prognosis in B-CLL.

Primary Adrenal Lymphoma with Chromosomal Abnormalities

Lymphomas developing in the adrenal glands are rare. Twenty-one cases of primary adrenal lymphomas have been reported in the English literature, but no cytogenetic data were given. We had the opportunity to examine three cases of primary adrenal lymphoma characterized by the B cell phenotype. Samples for histologic and immunohistologic diagnosis were obtained from postmortem examination in cases 1 and 2, and with an ultrasound-guided needle biopsy in cases 2 and 3. In all 3 cases, histologic examination of adrenal masses showed diffuse medium-sized cleaved lymphoma cells, which were positive for L-26, an immunohistochemical B cell marker. Endocrine studies showed adrenal insufficiency in 1 case. Cytogenetic examination showed clonal abnormalities, including 8q24 in case 1 and 14q32 in case 2, similar to those observed in nodal B cell lymphoma.

Cytogenetic evidence for clonal evolution in B-cell chronic lymphocytic leukemia

Sequential cytogenetic studies were performed in eight of ten patients with B-cell chronic lymphocytic leukemia presenting with trisomy 12 as the sole chromosomal abnormality. Follow-up studies of peripheral blood lymphocytes revealed that the karyotypes retained the sole abnormality of trisomy 12 in five cases, trisomy 12 converted to a normal karyotype during remission in one case, additional chromosome changes (-X,14q-) along with trisomy 12 appeared in one patient and multiple chromosome changes with or without trisomy 12 appeared in the remaining patient. The findings indicate that other chromosome changes in addition to trisomy 12 may develop as a result of clonal evolution or dedifferentiation, though the possibility that in two patients these changes may be related to chemotherapy and/or irradiation could not be ruled out entirely.