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.     

14q+ in Ph-positive chronic myelogenous leukemia

Two cases of chronic myelogenous leukemia with a Ph translocation and an additional chromosome change of the long arm of a chromosome #14 (14q+) are reported. The breakpoints on chromosome #14 were identified as 14q24 and 14q32, respectively. One of the patients did not show any evidence of blastic transformation; the other patient developed a myeloid blastic crisis when the abnormal 14q+ was seen in the bone marrow cells.     

Chromosomal characteristics of chronic and blastic phase of chronic myeloid leukemia. A study of 100 patients in India

We report the cytogenetic findings of 100 patients with chronic myeloid leukemia (CML) [72 patients in chronic phase (CP) and 28 patients in blastic phase (BP)]. Of the 95 Ph + patients, six had Ph variant translocations involving chromosomes 1, 6, 7, 10, and 12. The percentage frequency of patients with chromosomal changes other than Ph was 7.3%. The additional aberrations (e.g., + Ph, + 8, i(17q), and + 19 were observed in 66.6% of BP patients. Of these anomalies, the frequency of + Ph and + 19 was higher in our patients than the incidence reported in literature. The association of + Ph and + 19 in patients with extramedullary T-cell blast crisis is an unusual finding as compared with reports in the literature and could be explained by geographic heterogeneity. The extra chromosomal abnormalities were almost absent in lymphoid blast crisis patients with blast phenotype of common acute lymphoblastic leukemia (ALL) type. Discrepancies were noted in different tissues (bone marrow and lymph node) in patients with extramedullary blast crisis of both myeloid and lymphoid type. These findings indicate the cytogenetic correlation with clinical and morphological picture, which consequently implicates the diagnostic and prognostic significance of chromosomal aspects.     

Chromosomal abnormalities in lymphoid crisis of chronic myelogenous leukemia

The karyotypes in six patients with Ph-positive chronic myelogenous leukemia (CML) were investigated during the lymphoid crisis associated with high levels of terminal deoxynucleotidyl transferase (TdT) and/or the common acute lymphoblastic antigen (CALLA). Five of the six patients had only the Ph chromosome, with no other karyotypic abnormalities. The remaining one patient had a hypodiploid karyotype: 44,XY,?1,+der(1;?)(p22;?),?3,?4, ?6,?7,?8,?9,+22q?,+mar1,+mar2,+mar3. In four patients with lymphoid crisis expressing TdT and CALLA, the response to treatment with vincristine (VCR) and prednisolone (PRD) was satisfactory, except for the one patient whose karyotype was hypodiploid. A discussion is presented as to whether or not there is a correlation between the karyotypic changes, using banding methods, and TdT expression in patients whose blast cells were categorized morphologically as lymphoblastic at the onset of the blastic phase of CML. Sequential chromosome examinations during the chronic and blastic phases of CML were also performed in this study.     

Further cytogenetic evidence for a multistep pathogenesis of Ph-positive chronic myelogenous leukemia

A case of Ph-positive chronic myelogenous leukemia in blastic crisis was studied extensively by means of cytogenetic techniques. Karyotypic features, as well as growth patterns, kinetic data, and rates of sister chromatid exchange, were examined in bone marrow, blood, and pleural effusion cells. The data provide strong evidence for a multistep pathogenesis of the disease, the development of which appears to be linked to mechanisms of clonal selection and genetic imbalance in the malignant cell population.     

A t(11;21)(q13;q22) in Ph-positive chronic myelogenous leukemia

Reciprocal translocations, in addition to that of the Ph chromosome, though rare, have been reported in chronic myelogenous leukemia (CML). We describe here a case of Ph-positive CML with a new translocation, t(11;21)(q13;q22), and missing Y, which were present both during transformation to the blastic crisis and in the subsequent reversion to the chronic phase. The possible significance of this abnormality is discussed.     

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.     

Characterization of extramedullary tumors in a case of Ph-positive chronic myelogenous leukemia: possible involvement of immature T lymphocytes

A 42-year-old male with chronic myelogenous leukemia (CML) developed acute transformation associated with subcutaneous tumors. Histopathologic examinations of the tumors were done on two occasions; the first study revealed reticulum cell sarcoma-like features, and the second suggested a blastoma. Chromosomal analysis showed that the cells of the tumors originated from the CML clone. The cells had a negative reaction for myeloperoxidase by electron microscopy. Furthermore, biochemical and surface marker studies revealed that the tumor cells contained a significant terminal transferase activity. However, they did not express E- or EAC-rosette receptors, Ia-like antigens, or common ALL antigens.     

A case of near-triploidy in chronic myelogenous leukemia

A 61-year-old woman with chronic myelogenous leukemia (CML) in accelerated phase had a near-triploid bone-marrow karyotype. This karyotype is an unusual finding in CML, as we review 12 previously published similar cases. These patients do not differ clinically from other patients with CML in blast crisis. The cytogenetic features of near-diploid and near-triploid CML are similar, except that relative loss of chromosomes is more common and that isochromosome 17q has not been reported in near-triploid CML.     

bcr rearrangements in Philadelphia chromosome-positive acute lymphoblastic leukemia. A study of five Chinese patients in Taiwan

Cytogenetic studies were successfully conducted on 73 Chinese patients with acute lymphoblastic leukemia (ALL). A Philadelphia chromosome (Ph) was identified in four (9%) of the 46 children and in four (15%) of the 27 adults. None of these patients had any clinical features suggestive of chronic myelogenous leukemia (CML). Leukemic cells from five of the eight Ph-positive (Ph+) ALL patients were analyzed for bcr rearrangement by Southern blot analysis with three restriction enzymes and two bcr probes. One of the three children and both adult patients studied showed bcr rearrangement. Based on the data from the literature and the present study, 58% of adult and 14% of childhood Ph+ ALL patients demonstrated bcr rearrangement. There were no significant differences in clinical or laboratory findings between the two groups of patients with or without bcr rearrangement. Patients who had Ph+ ALL but no bcr rearrangement appear to have been victims of de novo acute leukemia, but it was still difficult to determine whether patients with bcr rearrangement had acute lymphoid transformation of subclinical CML. More studies and longer follow-ups are needed for clarification.