Sister chromatid exchange in normal and Ph1-positive leukemic cells after mitomycin-C treatment in vitro

The sister chromatid exchange (SCE) frequency was investigated in normal bone marrow and Ph1-positive cells of chronic myelocytic leukemia (CML) patients with and without mitomycin-C (MMC) treatment in vitro. Even though the spontaneous SCE frequency was found to be significantly lower in CML cells, the absolute SCE values after MMC treatment did not differ between leukemic and normal cells, and this seems to indicate an equilization of SCE rates. However, the fact that leukemic cells with lower spontaneous SCE rates need a further increase of SCE to reach values equal to those of normal cells might indicate a somewhat higher susceptibility of leukemic cells to DNA damage by MMC. This interpretation appears to be confirmed by the fact that the inhibition of cellular proliferation at higher MMC doses considerably reduced the number of leukemic cells that was able to divide twice during a given culture time.     

Some comments on sister chromatid exchange (SCE) in human neoplasia

The incidence of sister chromatid exchange (SCE) in bone marrow cells and/or lymphocytes of patients with various leukemias and the effects of drugs on the SCE incidence in the cells of patients with leukemia or cancer are presented and discussed. The possible use of SCE for screening antileukemic drugs, mutagenic and/or carcinogenic agents and susceptible human populations is presented.     

Growth rate and sister chromatid exchange (SCE) incidence of bone marrow cells in Acute Myeloblastic Leukemia (AML)

The sister chromatid exchange (SCE) incidence and growth kinetics have been studied by means of an in vitro bromodeoxyuridine (BrdU) chromosome labeling method in the bone marrow cells of 17 acute myeloblastic leukemia (AML) patients with only diploid cells at diagnosis, remission, and relapse of the disease. At diagnosis, the cells tended to exhibit a low SCE frequency as compared to that during remission. An increased SCE frequency was observed after chemotherapy during remission or relapse. At diagnosis and relapse, when leukemic blast cells predominated in the marrow, they were characterized by the predominance of cells that had undergone only one cell cycle after BrdU exposure. In contrast, the marrow cells during remission tended to resemble the control pattern of growth kinetics, with a predominance of cells undergoing second and third cell cycles in the presence of BrdU. These results suggest that the growth rate of leukemic and nonleukemic cells is different, and that chemotherapy can cause an increased SCE frequency in the marrow cells of AML patients irrespective of the state of the disease.     

Cell cycle analysis of stimulated lymphocytes of B-cell chronic lymphocytic leukemia

To clarify the cell cycle duration of stimulated cells in B cell chronic lymphocytic leukemia (B-CLL), sister chromatid differentiation (SCD) methodology was utilized. So-called polyclonal B-cell activators (PBA), i.e., staphylococcus bacteria strain Cowan I (Cowan I), pokeweed mitogen (PWM), Epstein-Barr virus (EBV), and lipopolysaccharide W from E. coli 055:B5 (LPS), were examined. Most metaphases on day 2 (48 hr) of culture were in first division (M1), and about half of the metaphases on day 3 (72 hr) of culture were in the second division (M2), and many of the metaphases on day 4 (96 hr) of culture were in the third division. These facts suggest that the optimal culture time for cytogenetic study of B-CLL should be 3 days or less to avoid in vitro artifacts.     

Chromosomes and causation of human cancer and leukemia. LII. Chromosome findings in treated patients with B-cell chronic lymphocytic leukemia

The chromosomes of stimulated lymphocytes in 40 treated cases of B-cell chronic lymphocytic leukemia (B-CLL) were examined. The polyclonal B-cell activators (PBA) used were: pokeweed mitogen (PWM), Epstein-Barr virus (EBV), and lipopolysaccharide W from Escherichia coli 055:B5 (LPS). Thirty-three (83%) of the 40 cases contained an adequate number of metaphases that were suitable for banding. Of 15 cases with abnormal clones, 7 cases had trisomy #12. Occasionally, trisomy #1, 6q?, i(7q), 14q+, trisomy #16, and trisomy #18 were seen. In 5 cases, marker chromosomes of unknown origin existed. The findings indicate that trisomy #12 may be a unique and nonrandom karyotypic change in B-CLL.     

Serial cytogenetic analysis of a recurrent malignant melanoma

A metastatic malignant melanoma in a 54-yr-old white female was examined cytogenetically on three different occasions. We found two different clones, one hypodiploid and another hypertriploid; however, both clones had the same markers [i.e., der(6),t(6;17), and der(17),t(1;17)]. Detailed analysis of the histopathology and clinical course suggests that these two different clones reflected different morphology and results of therapy.     

Possible specific chromosome changes in large bowel cancer

Structural and numerical changes affecting chromosomes number 7 and number 12 were the most frequent karyotypic changes observed in 10 large bowel cancers. The findings are briefly discussed in relation to the development of this malignancy.     

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 heavychain 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.     

Kappa and lambda immunoglobulin expression associated with abnormalities of chromosomes #2 and #22 in lymphoma and leukemia

The types of surface immunoglobulins on Burkitt lymphoma (BL) cells correlate with the specific chromosomes that are altered in the tumor. For example, BL with a t(2;8) translocation expresses kappa (kappa) light chains, whereas BL with a t(8;22) translocation expresses lambda (lambda) light immunoglobulin chains; these correspond with the locations of the kappa chain genes on chromosome #2 and the lambda chain genes on chromosome #22, respectively (1-5). In order to explain this close correlation between specific translocations and light chain expression in BL and BL-type acute lymphocytic leukemia (ALL) (L3 type), Hecht et al. [6] proposed the concept of position effect, which is reviewed herein.     

Chromosome 6 in malignant melanoma

Cytogenetic analysis of malignant melanoma (MM) cells from a number of cases revealed the frequent involvement of chromosome 6 in structural aberrations. The relevance of these findings to certain aspects of MM is briefly discussed.     

Two 14q+ chromosomes in malignant lymphoma: crucial cytogenetic changes on 14q

We encountered a 36-year-old white male patient with poorly differentiated lymphocytic lymphoma, whose lymph node cells showed a clonal cytogenetic change involving chromosome #14, i.e., 47,XY, + 2,der(14),t(14;14)(14pter----14q32;14q24----14q32++ +). In addition to this change, cells with a translocation between chromosomes #2 and another #14 [t(2;14)(q21;q24)], as well as a missing chromosome #8 were found. We have reviewed the literature dealing with two or more changes affecting chromosome #14 and discussed the importance of the cytogenetic change at band 14q32 in malignant lymphoma.     

Comparative results with various polyclonal B-cell activators in aneuploid chronic lymphocytic leukemia

The mitotic index and number of abnormal metaphases of cells stimulated with the various B-cell polyclonal mitogens (PBA) in six B cell chronic lymphocytic leukemia (B-CLL) cases were evaluated. The PBA included tetradecanoyl-0-phorbol-13-acetate (TPA), staphylococcus bacterial strain Cowan I (Cowan I), pokeweed mitogen (PWM), Epstein-Barr virus (EBV), and lipopolysaccharide W from E. coli 0.55:B5 (LPS). TPA could stimulate only 1 of 12 samples. Even though Cowan I led to a relatively high mitotic index, abnormal clones were inconsistently obtained with this mitogen. PWM, EBV, and LPS appear to be the most desirable activators of B-CLL cells among the PBA used in this study.     

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.     

Multiple cancers in a Turner's syndrome with 45,X/46,XXp-/46,XX/47,XXX karyotype

A female patient with a clinical picture of Turner's syndrome had five separate malignant tumors (three squamous cell carcinomas of the tongue, a colon cancer, and a glioblastoma multiforme). Her peripheral blood cells showed a 45,X/46,XXp-/46,XX/47,XXX mosaicism. The findings are discussed in relation to other extragonadal tumors in Turner's syndrome reported to-date.     

The cytogenetics of chronic myelocytic leukemia (CML): Chronic phase and blastic crisis

Some of the recent cytogenetic findings in chronic myelocytic leukemia have been summarized and the significance of the Philadelphia-chromosome, including those resulting from unusual translocations, and other karyotypic changes discussed in relation to survival, blastic phase (including its extramedullary origin), and therapy.     

Chromosomes and causation of human cancer and leukemia. XLVII. Severe hypodiploidy and chromosome conglomerations in ALL

A case of acute lymphoblastic leukemia (ALL) of the L1 type with severe hypodiploidy in the marrow cells (modal chromosome number, 36) is described. In addition, most of the metaphases contained chromosome conglomerations which consisted of varying numbers of chromosomes and appeared similar to conglomerations previously observed by us in a case of chronic myelocytic leukemia (CML) in the blastic phase (BP), where some cells contained less than 20 chromosomes. The karyotype of the ALL cells of our case was similar to those of published near-haploid ALL cases, possibly indicative of a common pathway of cytogenetic evolution.     

Acute myeloblastic leukemia (AML) with t(6;9) (p23;q34): A specific subgroup of AML?

A case of acute myeloblastic leukemia (AML) of M2 type in the FAB classification without Auer bodies in the leukemic cells was shown to have t(6;9)(p23;q34) in the marrow cells. Four hematologically similar cases with identical karyotype changes have been published. We propose, in support of others, that this may constitute a subgroup of AML characterized by a translocation between chromosome #6 and #9.