Length polymorphisms of the human Y chromosome in patients with chronic myelogenous leukemia

The extent of length heteromorphisms of the human Y chromosomes was measured in 50 patients with chronic myelogenous leukemia and was compared with 50 normal controls. No significant difference (p greater than 0.05) in the size of the Y chromosome was noted between these two groups. These findings differ from an earlier investigation, where a longer heterochromatic segment of Y chromosome was noted in malignant tumors and it was stressed that constitutive heterochromatin plays a role in susceptibility of cancer. Present investigation, however, suggests that this is not the case in patients with chronic myelogenous leukemia.     

Philadelphia chromosome negative acute lymphoblastic leukemia preceding Philadelphia positive chronic myelogenous leukemia

A patient with Philadelphia chromosome (Ph) negative acute lymphoblastic leukemia (ALL, FAB type L1) developed Ph-positive chronic myelogenous leukemia (CML) after more than 2 years in complete remission. Subsequently, Ph-positive lymphoblastic transformation occurred, which was again successfully treated. Thereafter, the CML state was interrupted twice more by blast crisis. The additional chromosomal abnormalities were atypical for Ph-positive CML. The course is interpreted as a possible example of the multistep development of CML. Blastic transformation occurring prior to the Ph chromosome has been reported in only two cases previously.     

Variant Philadelphia chromosome translocations in two patients with chronic myelogenous leukemia

Two patients with chronic myelogenous leukemia and new variant Philadelphia chromosome translocations are reported. In one case, a 41-year-old male, a 10;22 translocation was found in all bone marrow cells examined. Furthermore, the Y chromosome was missing in 90% of the analyzed metaphase cells. In the second patient, a 22-year-old male, all the marrow cells contained a complex rearrangement involving chromosomes No. 2, 9, and 22.     

Patient with chronic myelogenous leukemia and late appearing Philadelphia chromosome

The sixth example of a late appearing Ph¹ chromosome in a patient with typical chronic myelogenous leukemia is the subject of the present report. Knowledge of the true frequency of this apparently rare event awaits systematic longitudinal cytogenetic studies of patients with Ph¹-negative CML.     

Temporal association of marrow eosinophilia with inversion of chromosome 16 in recurrent blast crises of chronic myelogenous leukemia.

We report a patient with Ph+ chronic myelogenous leukemia (CML) whose recurrent blast crises were associated with marrow eosinophilia and inv(16). After intensive chemotherapy, for each blast crisis, the patient reentered chronic phase with disappearance of both the inv(16) and the eosinophilia.     

Effect of interferon-alpha on chromosome abnormalities in treated chronic myelogenous leukemia patients

To investigate the relationship of chromosomal aberrations at blastic crisis (BC) in chronic myelogenous leukemia (CML), with previous therapies and with atomic bomb (AB) exposure, we studied 114 CML patients who developed BC, including 23 AB survivors in Hiroshima. In total, only 45.6% showed major-route abnormalities, which figure was far lower than those previously reported, implying possibility of geographical difference. Occurrence of major-route abnormality was not associated with either duration of chronic phase or survival time after BC. Patients treated with interferon-alpha (IFNalpha) showed lower frequency of major-route abnormalities and lower number of abnormal chromosomes than did patients treated with busulfan (Bu). The frequency of trisomy 8 was lower and monosomy 7 was higher in IFNalpha-treated than in Bu-treated patients. The frequency of unusual abnormalities at BC in IFNalpha-treated patients was indistinguishable from those in Bu-treated patients and, notably, a more common (40%) feature in IFNalpha-treated patients was no change in the cytogenetic picture. Thus, we conclude that IFNalpha action on chromosome aberration is basically quite neutral and that IFNalpha does not induce any specific aberrations, including unusual ones at BC, with an exception of deletion of chromosome 7. Atomic bomb exposure status did not make any difference in secondary abnormalities at BC.     

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.     

Enhanced expression of chromosome fragile site 10q25 in chronic myelogenous leukemia

Spontaneous expression of a BrdU-sensitive fragile site at 10q25 was observed in normal lymphocytes and malignant blood and bone marrow cells in chronic myelogenous leukemia (CML). The cells were marked by a Philadelphia chromosome rearrangement due to insertion of 22q11----q13 at 11q13. The fragile site at 10q25 was expressed in larger proportions of malignant than normal cells. Although this fragile site is not at a cancer chromosome breakpoint, malignancy enhanced its expression, consistent with a cascade effect.     

Breakpoint cluster region rearrangements in chronic myelogenous leukemia with a masked Philadelphia chromosome

Cytogenetic and molecular analyses were performed in a case of chronic myelogenous leukemia. The cytogenetic study revealed that the leukemic cells of this patient contained a three-way translocation involving chromosomes #5, #9, and #22, resulting in a masked Philadelphia chromosome; the karyotype of the leukemic cells was 46,XY,t(5;22;9)(q31;q11;q34). Southern blot analysis of leukemic cell DNA was performed using a 1.1 kb HindIII-EcoRI breakpoint cluster region (bcr) probe. The results showed that BglII digested DNA showed two abnormal bcr fragments (i.e., 5.2 kb and 2.7 kb) in contrast to the results with DNA from two patients with a standard Ph chromosome [t(9;22)(q34;q11)] who showed one normal 5.0-kb bcr fragment in addition to altered fragments of about 4.3 kb or 4.0 kb. Bam HI digests of DNA from the leukemic cells of the patient with the masked Ph chromosome showed two bands (3.3 kb and 6.5 kb), whereas, DNA from the two patients with standard Ph translocations showed only a 3.3-kb bcr fragment. The results indicate that the molecular events in a masked Ph affect the bcr locus in a manner similar to that seen in standard Ph chromosomes.     

Inversion of chromosome 3 in a case of chronic myelogenous leukemia with abnormal thrombopoiesis

A patient with chronic myelogenous leukemia (CML) associated with a remarkable increase of micromegakaryocytes in bone marrow was revealed to have an abnormality of a long arm of chromosome #3, i.e., inv(3)(q21q26), in addition to a complex Ph translocation: t(9;22;15)(q34;q11;q22). Although several cases of acute leukemia with inv(3)(q21q26) and abnormal megakaryocytes have been reported, this is the first case in which the association of inv(3)(q21q26) with a megakaryocytic abnormality was observed in a patient with CML. Our findings suggest that this structural rearrangement may be more specifically associated with abnormal thrombopoiesis than are other structural anomalies of 3q.     

Cytogenetic peculiarities in chronic myelogenous leukemia

Cytogenetic investigations were performed in 185 patients with chronic myelogenous leukemia (CML) at all stages of the disease; 166 patients were Ph positive-159 (95.8%) of these showing the standard Ph translocation, and 7 (4.2%) variant translocations-17 patients were Ph negative. In 2 patients the cytogenetic analysis was unsuccessful. Additional aberrations were found in 40 (24.1%) of the Ph-positive patients. Nine (52.9%) of the Ph-negative patients showed chromosome anomalies. Besides the well known nonrandom abnormalities (-7, +8, i(17q), +19, +Ph) we found a high frequency of clones with rare or not yet described structural rearrangements--in 14 cases (34.2%) of the Ph-positive patients and in 2 cases (20%) of the Ph-negative patients with other chromosome abnormalities. The clinical significance of these findings is discussed.     

Complex translocation involving Ph chromosome in a patient with typical chronic myelogenous leukemia.

We report a cytogenetic study of a patient with chronic myelogenous leukemia (CML) who, while displaying a Philadelphia (Ph) chromosome, resulting from a standard t(9;22) at diagnosis, during the chronic phase (CP) showed disappearance of the Ph and occurrence of new chromosome changes, including a marker probably arising from a translocation involving chromosome 17 and the Ph. In situ hybridization confirmed the cytogenetic appearance and demonstrated that the breakpoint on the Ph marker occurred below the BCR-ABL fusion gene.     

内蒙古地区慢性粒细胞白血病患者HLA-A基因多态性的研究

目的探讨人类白细胞抗原（human leukocyte antigen,HLA）HLA-A、等位基因多态性与CML白血病的相关性。方法采用Luminex流式技术-序列特异性寡核苷酸探针反向杂交（flow cytometry-sequence specific oligonucleotideprobe,FLOW-SSOP）方法对内蒙地区39例慢性粒细胞白血病chronic myeloid leukemia,CML）患者HLA-A等位基因多态性进行分析,以北方地区健康群体资料作为正常对照。结果在慢性粒细胞白血病中,HLA-A＊02XX,＊11XX A＊6601（RR=21.459）等位基因频率高于对照组,差异有统计学意义（P〈0.05）;A＊33XX等位基因频率明显低于对照组（P〈0.05）;其它等位基因频率在两组之间差异无统计学意义。结论HLA-A＊02XX,A＊11XX,A＊6601等位基因与CML呈正相关,而HLA-A＊33XX等位基因与CML呈负相关。