Surabhi Kakati

Chromosomes and causation of human cancer and leukemiaXVI. Banding studies of chronic myelocytic leukemia, including five unusual Ph1translocations

Forty‐two Ph1‐positive cases of chronic myelocytic leukemia (CML) were examined with chromosomal banding techniques. Thirty‐seven of these cases had the “standard” type of Ph1 translocation between chromosomes #9 and #22 [t(9;22)(q34;q11)] in the Ph1‐positive marrow cells; 5 cases had unusual types of Ph1 translocation. Of the 37 cases, 21 had additional numerical and/or structural chromosomal changes, 2 had a missing Y chromosome, and 1 had an extra Ph1 in the Ph1‐positive cells. In the 5 cases with unusual types of Ph1 translocation, chromosomes #2, #9, #10, and #13 were involved. The clinical picture in these 5 patients did not differ materially from that of the other Ph1‐positive patients with CML, probably indicating that the recipient chromosome, with which the translocation from #22 takes place, does not play a crucial role in the course of the CML. In the 21 cases with abnormal karyotypes, nonrandom chromosomal changes were observed. Most of the changes were related to events occurring at the centromeric region. The prognosis of cases with only an extra #8 or Ph1 appears to be better than that for cases with an iso‐17q [i(17q)] chromosome or other extra chromosomes. The presence of the Ph1 (deleted #22) in every case points to the essentiality of this karyotypic findings in the diagnosis of CML and possibly in the genesis of the disease.

Chromosomes and causation of human cancer and leukemia. L. Cytogenetics of leukemias complicating other diseases

Complicating (secondary) leukemias in 20 patients, 18 of whom had various forms of neoplasia treated with chemotherapy and/or radiation, have been examined in regard to the karyotypic findings present in the leukemic cells of the marrow. In addition, the published cases of complicating leukemia have been tabulated. Based on the results of the present study and those in the literature it appears that chromosomes #3 and #17 should be stressed as being nonrandomly involved in complicating leukemia in addition to the previously stressed chromosomes #5 and #7. The results of the present study are discussed in relation to those reported in the literature, and stress put on the significance of cytogenetic changes in relation to possible causative factors of the complicating leukemia. The hypothesis is advanced that these nonrandom chromosome changes may reflect causative specificity of the complicating leukemia and that a concerted effort must be made to obtain more cogent information on the role of noxious agents in the causation of complicating leukemia.

Chromosomes and causation of human cancer and leukemia. XXII. Karyotypic changes in malignant melanoma.

Detailed karyotypic analysis with G‐ and C‐banding has been performed on cells of four malignant melanomas. The modal number in two cases was in the hypodiploid range, the chromosome numbers varying from 39 to 43. These two tumors had 5 to 13 marker chromosomes. The other two tumors were in the polyploid range, with modal numbers of 63 to 157 chromosomes. The cells had a minimum of 11 and a maximum of 40 marker chromosomes. Chromosome #1 was more frequently involved in aberrations than any other chromosome. The most common breakpoints on this chromosome were 1q21, 1q25 and 1q32. Frequent breakpoints were also noticed in the centromeric region in various chromosomes. In chromosome #1, however, the centromeric area does not seem to be involved. The more common breakpoints on the various chromosomes were 1q21, 1q25, 1q32, 5p13, 9q13, 11q23, 12q13. No common markers were noticed among these four cases of melanoma, but are noticed in unrelated tumors.

The chromosomes and causation of human cancer and leukemia. XIX. Common markers in various tumors.

Most human cancers are associated with abnormal (marker) chromosomes. In past and present studies banding analyses have uncovered a much larger number of markers in cancer cells than was seen with standard (Giemsa) staining. Furthermore, common markers of identical morphology and origin were found in tumors of related or unrelated tissues or organs, suggesting that in all probability such markers, although present in cancers of diverse nature, may indicate a common etiology, either related to the causation of the cancers, to the progression of the tumors, or to the predilection of certain chromosomes to undergo morphologic changes leading to marker formation. Even though some markers were common to different tumors, the bulk of the markers in the cancers studied could not be identified with certainty and their nature varied from tumor to tumor.

Chromosomes and causation of human cancer and leukemia. XLI. Cytogenetic experience with non-hodgkin, non-burkitt lymphomas

Abstract Twelve cases with non-Hodgkin, non-Burkitt lymphoma were studied cytogenetically, primarily with material obtained through bone marrow aspiration. An evaluation of the use of bone marrow material for karyotypic studies in lymphoma revealed it to be a rather unfruitful approach in that successful cytogenetic findings were obtained in less than 10% of all newly diagnosed cases of lymphoma observed during a period of several years. It would appear that the utilization of lymph node material or material obtained from tissues frequently and extensively involved by lymphoma (e.g., spleen) yield significantly more successful results than bone marrow material. The cytogenetic findings encountered were similar to those recently summarized for lymphoma and included, among others, three cases with 14q+, two cases with 6q−, two cases with iso-8q, one case with an iso-6p chromosome. Of interest was the demonstration of karyotypic changes compatible with those in lymphoma in two cases where the presence of a complicating acute myeloblastic leukemia or other acute leukemia was suspected. In addition, definitely abnormal cells compatible with those seen in lymphoma were found in the marrow of a patient in whom cytologic examination failed to reveal their presence. From these findings it is apparent that cytogenetic findings can be used as important diagnostic aids in some patients with lymphoma with complicated and/or uncertain histologic and clinical manifestations.

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

Abstract 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.

Chromosomes and causation of human cancer and leukemia. XIV. Origin of a large number of markers in a cancer

A cancerous effusion from a patient with cancer of the breast, with a high modal number of chromosomes (81–83) and with 11–13 abnormal chromosomes (markers) of eight different origins, has been examined in detal karyotypically with C‐, G‐, and Q‐banding techniques. Except for a rare chromosome, all the normal chromosomes were identified and, more importantly, the origin of all markers was ascertained. This study indicates the feasibility of identifying all the chromosomes in cancer cells, even in those with highly polyploid and complicated chromosome constitutions.

Cytogenetic findings in a primary adrenocortical carcinoma

Cytogenetic analysis of a primary adrenocortical carcinoma revealed clonal rearrangements of several autosomes and sex chromosomes. In all metaphases the following marker chromosomes were present: 4p+,t(3;12)(p14;p13),14q+, t(15;20)(p11;q11), t(5;18) (p13.3;p11.2), psu dic(18)t(18.3)(p11.39;p12), and psu dic(20)t(20;9)(q11.2;p11). The results are discussed in relation to the cytogenetic findings in other solid tumors, especially of the kidney.

Chromosomes and causation of human cancer and leukemia. LI. A hairy cell leukemia case with 14q+ and ring chromosomes: Significance of ring chromosomes in blood disorders

What appears to be the first hairy cell leukemia case with a 14q+ anomaly is described. In addition to the 14q+ anomaly, a 6q- and a ring chromosome were seen in a blood sample stimulated with lipopolysaccharide, a B-cell mitogen. The clinical course of the present case was short, stormy, and had a poor response to therapy. The correlation between the clinical course and the presence of a ring chromosome in myelo- and lymphoproliferative blood disorders is discussed in relation to the various blood disorders with this karyotype anomaly described in the literature.

Use of radiation induced chromosomal damage in human lymphocytes as a biological dosimeter is questionable.

Using dicentric chromosomes and acentric fragments as indicators of radiation sensitivity, a study has been performed on human lymphocyte chromosomes by irradiating peripheral blood cells at G0. Donor-to-donor variation has been noticed regarding radiation sensitivity even when metaphase spreads were scored at the first cell cycle. Thus, it appears that, at the present state, use of chromosomal damage in peripheral blood cell cultures as an effective biological dosimeter for effects of radiation is questionable.