Chromosomes in the chronic phase of chronic granulocytic leukemia

Chromosomal analysis of 66 cases with chronic granulocytic leukemia (CGL) was performed using Q- and G-banding techniques. In 65 of the 66 cases, a Philadelphia (Ph¹) chromosome with evidence of translocation was observed. Karyotypic abnormalities in addition to the Ph¹ were found in 21 cases. In 6 of these 21 cases, the chronic phase persisted for more than 1 year after the first appearance of these abnormalities; in the remaining 15 cases, the abnormalities appeared shortly before or during the acute phase. Of the 6 cases with karyotypic abnormalities in addition to the Ph¹ in the chronic phase, 3 cases had trisomy #8 and the other 3 cases had a double Ph¹, a translocation between chromosomes #4 and #9, and loss of the Y chromosome, respectively. In contrast to the 3 cases where trisomy #8 was found in the chronic phase and exhibited no other abnormalities besides the extra #8 and a Ph¹, all 5 cases whose trisomy #8 was found in the acute phase showed one or more additional chromosomal changes besides the extra #8 and the Ph¹. In the former 3 cases, the percentage of metaphases with trisomy #8 increased gradually throughout the chronic phase during low dose busulfan therapy. One patient in the chronic phase for more than 14 months had only one extra Ph¹. In contrast, all of the 7 cases with double Ph¹ chromosomes shortly before or in the acute phase showed one or more additional chromosomes in addition to double Ph¹. The significance of a double double Ph¹ in the chronic and acute phases appears to be similar to that of trisomy #8 in the respective phases. The observation of trisomy #8 and double Ph¹ might prove to be a useful clinical indicator of the progression of CGL.     

Erythrocyte glutathione reductase activity and acquired trisomy #8 in various hematologic disorders

The gene for erythrocyte glutathione reductase (E-GR) activity has been assigned to chromosome #8. In the present series, we examined the E-GR activity in 14 cases with chronic myelodysplastic syndrome (CMS, preleukemia), atypical acute myelogenous leukemia (AML), or chronic myelogenous leukemia (CML), with and without acquired trisomy #8. No difference in the incidence of high levels of this enzyme was found between two groups, i.e., those with and without trisomy #8 suggesting the existence of a complex regulatory system in addition to chromosome #8.     

Chromosomal abnormalities in chronic lymphocytic leukemia

Peripheral blood lymphocytes from five chronic lymphocytic leukemia (CLL) patients were cultured with PHA for 3-6 days. Chromosomal analysis with G-banding showed 25% of the diploid metaphases were pseudodiploid as a result of either a chromosomal deletion or a translocation. Abnormal clones with 18p- were seen in two patients, and two other patients had 18p- metaphases, but with other inconsistent abnormal chromosomes. None of the patients had trisomy 12, which has been thought by some to carry a poor prognosis. Although no conclusion can be reached regarding the significance of the chromosomal abnormalities in CLL, the type of chromosomal abnormalities in these patients suggests that they are the result of chromosomal breakage and abnormal repair.     

Extreme hypodiploidy in a case of myelomonocytic crisis of chronic myelogenous leukemia

Two cytogenetically distinct populations of marrow cells were observed in a 28-year-old woman who developed a fulminant blastic crisis (BC) of chronic myelogenous leukemia (CML) after only 1 year in the chronic phase: one population with 35-36 chromosomes, the other showing 66-72 chromosomes. Cytochemical investigation demonstrated a myelomonocytic type of BC. Chromosome banding and correlation analysis of the mean karyotypes of the two populations showed that a close relationship existed between them, indicating that one population had developed from the other. The cytogenetic evidence suggests but does not prove that the cells with triploid chromosome numbers developed from the extremely hypodiploid population by duplication of the chromosome complement. The extreme cytogenetic diversity of both populations indicates that each was undergoing further cytogenetic evolution.     

Chromosome 14q+ in adult T-cell leukemia

Cytogenetic studies were performed on leukemic cells from two patients with adult T-cell leukemia. A 14q+ marker chromosome was found in the peripheral blood leukocytes from patient No. 1 and in a leukemic T-cell line (MT-1) derived from the peripheral blood of patient No. 2. The 14q+ resulted from a t(12;14) in patient No. 1 and from a t(Y;14) in patient No. 2 with a break point at 14q32 in each case. In addition, the leukemic cells from patient No. 1 showed a t(1;7) and a 9q-, while the MT-1 line had numerous structural abnormalities. Thus, it is clear that a 14q+ translocation is not restricted to B-cell neoplasms but occurs in T-cell neoplasms as well.     

Cytogenetics of chronic B-cell and T-cell leukemia

Chromosome data in chronic lymphocytic leukemia (CLL) are sparse. In the common form, B-cell CLL, the neoplastic cells do not usually proliferate in vitro, and apparently most reports of “normal” cytogenetic patterns reflect nonneoplastic T cells dividing in mitogen-stimulated cultures. Until better methods are developed to stimulate proliferation of CLL B cells, the nature and frequency of chromosomal abnormalities in this disorder will remain largely unknown. Chronic T-cell leukemias constitute a rare and heterogeneous group of dyscrasias, ranging clinically from typical CLL to variants of the Sezary syndrome. The neoplastic lymphoeytes respond to T-cell mitogens, and in a series of nine patients, all had cytogenetically altered clones in the peripheral blood. Banding revealed nonrandom involvement of chromosomes 2, 14, and 18, with a 14q+ marker in two cases. Sequential studies in this series have demonstrated karyotypic changes over time, correlated, in some patients, with clinical course or alterations in the lymphocytes; but the general prognostic value of such investigations remains to be determined.     

Chromosomal anomaly of 6q in chronic myelogenous leukemia (CML)

Anomalies of chromosome 6q, along with other chromosomal anomalies, are described in the bone marrow cells of two patients with chronic myelogenous leukemia (CML). One patient, a 14-year-old male, developed the karyotype 46,XY,t(1;6)(p36;q15),del(3)(q25),del(17)(p11),? inv(17)(q12q24) during blastic crisis of his disease. The other patient, a 24-year-old male, had the karyotype 46,XY,del(6)(q13),t(9;22)(q34;q11) during the early phase of his disease and evolution of i(17q) in the karyotype late in the disease.     

Near-haploid cell line in the blastic crisis of chronic myelogenous leukemia: A possible marker for lymphoid malignancy

The blast cells of a 14-year-old patient in the blastic phase of chronic myelogenous leukemia (CML) were studied. Cellular morphology, presence of the enzyme terminal deoxynucleotidyl transferase (TdT), and reactivity to the common acute lymphoblastic leukemia antiserum (CALLA) substantiated a lymphoid blast cell line. Immunologic surface markers were nonreactive for E-rosette (T) cells and immunoglobulin-bearing (B) cells. Cytogenetic studies revealed persistance of the Philadelphia chromosome and a near-haploid cell line, i.e., 28,XY,t(9;22),+14,+15,+21,+22(GTG).The patient responded to chemotherapy with vincristine, prednisone, and l-asparaginase, first line drugs used for remission-induction of acute lymphoblastic leukemia in childhood. We suggest that severe hypodiploidy or near-haploidy, along with TdT and CALLA, may provide more accurate prognostic information in patients with CML and the lymphoid blastic crisis.     

Chromosomal breakage and sister chromatid exchange in peripheral blood lymphocytes and lymphoblastoid cell lines in the X-linked lymphoproliferative syndrome

The frequencies of chromosomal aberrations and sister chromatid exchange (SCE) were measured in lymphoblastoid cell lines (LCLs) and in phytohemagglutinin (PHA)- and pokeweed mitogen (PWM)-stimulated lymphocytes from males with X-linked lymphoproliferative (XLP) syndrome, their obligate carrier mothers, and control subjects. We observed an increased frequency of chromosomal aberrations including increased polyploidy in LCLs derived from families with XLP with time in culture. The SCE rate in LCLs (mean of 3.89 SCEs per cell) was much lower than that in PHA- or PWM-stimulated lymphocytes: PWM-stimulated lymphocytes showed 9.58 SCEs per cell and PHA-stimulated cells had 11.38 SCEs per cell. A greater number of chromosomal gaps and breaks in the D-group chromosomes of LCLs of affected males and carrier females were identified compared to the number expected, based on chromosomal length and the number of aberrations seen in PHA-stimulated cell cultures. No differences in the frequency of SCEs or chromosomal aberrations were found in control subjects and affected males or carrier females in the peripheral lymphocytes stimulated by PHA. Phenotypes of XLP appear to arise from failure of immune responses to Epstein-Barr virus (EBV) and not from intrinsic chromosomal breakage or instability.     

Absence of heteromorphism of chromosome #2 homologues in patients with hereditary adenomatosis of the colon and rectum

Measurement analysis of lymphocyte prometaphase chromosomes from three patients with hereditary adenomatosis of the colon and rectum could not confirm the heteromorphism of chromosome #2 homologues, which was suggested by Gardner et al. Instead, the analysis showed to what extent individual homologous pairs are "heteromorphic" quantitatively.     

Bronchial extramedullary hematopoiesis preceding chronic myelogenous leukemia

Extramedullary hematopoiesis of the bronchus is rare. The case of a 72-year-old man in whom the right lower lobe bronchus was obstructed by extramedullary hematopoiesis is presented. Ten months after the initial presentation, Philadelphia chromosome-negative chronic myelogenous leukemia was diagnosed. Such findings have not been reported previously. The various anatomic locations of extramedullary hematopoiesis are reviewed, with an emphasis on intrathoracic and pulmonary presentations. The clinical and pathologic features and the differential diagnosis in the present case are discussed.     

Leukocyte concentration and the yields of metaphase cells in cultured peripheral blood of leukemic patients with hyperleukocytosis

The optimal concentration of leukocytes for maximizing the yields of metaphase cells was examined using PHA-stimulated and unstimulated peripheral blood cells of various leukemic patients with hyperleukocytosis, including 5 acute nonlymphocytic leukemias, 4 Ph-positive chronic myelocytic leukemias, one acute lymphoblastic leukemia, and one malignant lymphoma at a leukemic phase. The yields of metaphases reached maximum at leukocyte concentrations of either 1 × 10⁶ or 2 × 10⁶/ml in both stimulated and unstimulated blood cultures of each patient, except for one patient with malignant lymphoma who exhibited no metaphases at any cell concentration level in the unstimulated culture. Metaphase yields in the stimulated and unstimulated cultures correlated with neither the percentages of blast cells and lymphocytes in the peripheral blood of the leukemia patients nor with the type of leukemia studied.     

Chronic myelogenous leukemia with a complex Ph1 translocation in an XYY male

We encountered a 38-year-old Japanese male patient with chronic myelogenous leukemia (CML), whose bone marrow and peripheral blood cells during the chronic and blastic phases contained a complex Ph¹ translocation and an extra Y chromosome [i.e., 47,XYY,t(9;22;13)(q34;q11;q14)]. A karyotypic analysis of PHA-stimulated lymphocytes showed the constitutional karyotype to be 47,XYY. Thus, it was considered that CML with a complex Ph¹ translocation developed in an XYY male; such a case has not been reported, so far. A B-lymphocyte cell line with the complex Ph¹ translocation was established by the procedure of Epstein-Barr virus transformation. The presence of the complex Ph¹ translocation in the B-lymphocyte cell line suggests that some of the B lymphocytes in this patient originated from the CML clone.     

Chromosomal banding patterns in patients with acute nonlymphocytic leukemia

Approximately 50% of acute nonlymphocytic leukemia (ANLL) patients studied with banding techniques have detectable clonal karyotypic abnormalities. Although there is considerable variability, certain nonrandom abnormalities are observed, including trisomy 8, monosomy 7, and the 8;21 translocation (frequently accompanied by loss of an X or Y). The 15; 17 translocation is highly specific for acute promyelocytic leukemia. Clonal evolution of the karyotype can be observed in a significant number of ANLL patients for whom serial cytogenetic analyses are obtained. Gain of a No. 8 is the most frequently observed evolutionary change. Bone marrow cells from patients who develop ANLL following treatment of a previous malignancy often have hypodiploid modal numbers and frequently show loss of all or part of a chromosome No. 5 or No. 7.     

Chromosomal evidence of a common stem cell in acute lymphoblastic leukemia and chronic granulocytic leukemia

A patient with acute lymphoblastic leukemia (ALL) was found, at the time of diagnosis, to have an unusual Philadelphia chromosome (Ph¹) with a satellite marker. The disease evolved into the chronic phase of chronic granulocytic leukemia (CGL), with persistance of the marker. Two months later, the patient died of ALL.     

Amplification and abnormal chromosomal distribution of ribosomal genes (rDNA) in rat erythroleukemia cells

The ribosomal cistrons (rDNA)/genome ratio was measured in five cell lines derived from three chemically induced erythroblastic leukemias (D-1, D-2, and NE26) in the Long-Evans (LE) rat and compared with values in the normal liver, bone marrow, and fetus. The ratio was 20–42% higher in the leukemias than in normal tissues. The number of autoradiographic silver grains of ¹²⁵I-labeled rRNA hybridized in situ over three nucleolus organizer regions (NORs) of leukemia cells was determined and compared with that of the normal cells. Although the distribution of silver grains of normal cells averaged 44.6%, 25.9%, and 29.5% in NORs of chromosomes #3, #11, and #12, respectively, their distribution was abnormal in two of the leukemias examined; rDNA was amplified in chromosomes #12 of two sublines (K1DA and K1DB) of one leukemis (D-1), and in one chromosome #3 of two sublines (K2D and K3D) of another leukemia (D-2). We consider the possibility that these abnormal patterns of rDNA distribution are related to the increase in rDNA in leukemia cells.     

Chromosome abnormalities in acute lymphoblastic leukemia

Less information is available on the cytogenetic abnormalities in marrow cells of patients with acute lymphoblastic leukemia (ALL) than on abnormalities in acute nonlymphocytic leukemia (ANLL); nonetheless, some patterns of karyotypic change in ALL are evident. Even with banding, about 50% of patients appear to have a normal karyotype. The modal chromosome number tends to be higher in ALL than in ANLL. Every patient with B-cell ALL has had an abnormality of one chromosome No. 14 that involved the translocation of material to the end of the long arm. Among seven reported cases, the translocation was from 8q in three patients and 11q in one. Cells with a haploid or near-haploid (24–35) chromosome number have been reported in five patients with ALL and in four patients in a lymphoid blast crisis of chronic myelogenous leukemia. The karyotype in the four ALL patients whose cells were analyzed with banding was remarkably consistent. All patients had the haploid number, usually with both sex chromosomes, plus an additional No. 10, 18, and 21. Evolution of the karyotype, which occurs in the leukemic cells of about 50% of patients, involves cells of patients who had an initially normal or an initially abnormal karyotype. The evidence regarding a correlation between the presence of an abnormal clone prior to treatment and response to treatment is contradictory at present. Some chromosome abnormalities, such as the presence of a Philadelphia (Ph¹) chromosome, a 14q+ chromosome, or a haploid clone, are associated with a relatively short survival.     

Out-of-phase separation of a G-group chromosome in a woman with chronic myelogenous leukemia

This report describes a case of out-of-phase (premature) centromere separation of a G-group chromosome in bone marrow cells of a woman with Ph1-negative, chronic myelogenous leukemia. Attention is drawn to the occurrence of this new cytogenetic anomaly in human disease.