Chromosomes and causation of human cancer and leukemia. LIII. Comprehensive cytogenetic analysis of an erythroleukemia

A comprehensive cytogenetic analysis has been performed in a case of erythroleukemia (EL), M6 in the FAB classification. A bone marrow sample was shown to be characterized by an unusually high degree of polyploidy with the presence of a dominating hypotetraploid clone. G-banding analysis revealed extensive structural rearrangements involving chromosomes #1,#3,#12,#16,#17, and #21. The SCE frequency was higher in the cells of the dominant clone when compared to that of near-diploid, presumably nonmalignant cells. Cell cycle analysis revealed that the hypotetraploid cells progressed through the cell cycle much slower than did the near-diploid cells.     

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.     

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.     

Cytogenetic findings in congenital leukemia: case report and review of the literature

The cytogenetic findings in a five-week-old female infant with acute lymphoblastic leukemia (ALL) are reported. Markers 11q - and 19 + were observed and considered to be due to an interstitial deletion of segment 11q13 to 11q23 of chromosome #11 and an insertion of this segment into the terminal region of the short arm of #19. Previously published banded cases of leukemic infants under one year of age have been summarized. A review of the data in these 29 cases suggests that the appearance of a normal karyotype in acute leukemia of infants (less than or equal to 1 year old) is much less common than in other categories of acute leukemia. Fourteen out of 29 cases (48%) had chromosomal abnormalities involving 11q. Seven of eight ALL cases had aberrations with a breakpoint at 11q22-23; six cases had t(4;11), one case had a del(11q) and ins(19p), and another had a t(1;22;4). All of three AMMoL cases had translocations involving the long arm of #11. The percentage of patients with t(4;11) and certain translocations involving 11q in infants with ALL or AMMoL, respectively, is higher than that seen in ALL and AMMoL in general. Eleven out of 12 cases (92%) of infant acute leukemias with chromosomal abnormalities involving 11q22-23 were five months old or less.     

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.     

Karyotypic findings in a case of prolymphocytic leukemia with a history of radiation exposure

Cytogenetic examination, utilizing B- and T-cell mitogens, of the peripheral blood lymphocytes of a patient with the prolymphocytic variant of chronic lymphocytic leukemia (CLL) and a history of radiation exposure revealed two abnormal clones. One clone with 48 chromosomes (+t(6;12),6q-, +12,14q+) may be derived from CLL cells, whereas the clone with 46 chromosomes and a ring #11 possibly originated from normal T and/or B cells affected by past irradiation.     

Trisomy X as a possible initial chromosome change in a gastric cancer

Primary and metastatic gastric tumors from a patient previously treated for five different cancers were cytogenetically examined by G-banding. Both types of tumors had cells with a 47,XX,+X karyotype; in addition, the primary tumor had a second clone with a 48,XX,+X,+12 karyotype. No other abnormality was found in either tumor. The lymphocytes of this patient revealed a normal female diploid karyotype.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Complex cytogenetic findings in acute leukemia

Although certain types of acute nonlymphocytic leukemia (ANLL) are now characterized by specific chromosome translocations, certain other cases of ANLL elude simple cytogenetic classification. We describe here a case of acute myelomonocytic leukemia with a complex and unusual karyotype picture including double minutes, three definite translocations, two other possible translocations, and additional morphologic and numerical chromosome changes. The three definite translocations were t(2;11), t(2;12), and t(5;15), fitting the criteria of major karyotype abnormalities. These complex and unusual chromosome findings may relate to the rapid course of the disease.     

Sister chromatid exchange levels and cell cycle time in human bone marrow cells and lymphocytes

The frequency of sister chromatid exchange (SCE) and the cell-cycle-specific pattern of mitoses were analyzed at the same time in normal bone marrow cells and lymphocytes of six healthy donors. The SCE frequency was found to be significantly higher in lymphocytes. The cell-cycle-specific pattern revealed significantly shorter cell cycle times for normal bone marrow cells as compared with those of phytohemagglutinin (PHA) stimulated lymphocytes. Chromosomes of bone marrow metaphases displayed a more contracted morphology.