A new variant translocation (19q plus, 22q minus) in chronic myelocytic leukemia

A translocation between chromosome 19 and chromosome 22 was found in one out of nine patients with CML. All the remaining eight patients demonstrated a translocation between chromosomes 9 and 22. The clinical pattern of the disease was similar in the patient with the translocation between chromosomes 19 and 22 and in the other CML patients. Thus the presence of the Ph¹ chromosome appears to be more important for the course and pattern of the disease than the location of the translocated fragment.     

Minute chromosomes in a case of chronic Ph1-positive myeloid leukemia

Minute chromosomes (mins) were found in all bone marrow cells in a 62-year-old woman with Ph1 positive chronic myeloid leukemia. The cells had a range of 39 to 50 chromosomes with a mode of 46. The examined metaphases had a variety of numerical and structural chromosome abnormalities, as well as 2 to 6 minute chromosomes. Our case supports the assumption that there may be a correlation between the presence of mins in leukemias and the resistance of the cells to chemotherapy or the rapid progression of the disease.     

Role of heterochromatin during preferential 9q;22q translocation in chronic myelogenous leukemia

The secondary constriction region (h) of human chromosome 9 was evaluated in 55 chronic myelogenous leukemia (CML) patients with respect to its size and position. Each case was examined by C-banding and distamycin A-4,6-diamidino-2-phenylindole techniques for the expression of the h regions. When one h region of chromosome 9 was larger, it was more frequently involved in the reciprocal translocation with chromosome 22. In addition, there was a higher incidence of pericentric inversions in the h regions in the translocated chromosome 9 when compared with normal homologues. The role of the constitutive heterochromatin of chromosome 9 as a possible influencing factor during 9q;22q translocation in CML is suggested.     

Translocation between chromosome 7 and chromosome 22, t(7;22)(p22;q12), in a patient with chronic myelocytic leukemia

Summary A 46-year-old man with chronic myelocytic leukemia had a new variant translocation between chromosome 22 and chromosome 7 in bone marrow cells. No involvement of chromosome 9 was seen. The patient entered blastic transformation within half a year, by which time he had acquired an isochromosome 17 in addition to the variant translocation.     

Blast crisis of Philadelphia chromosome-positive chronic myelocytic leukemia (CML). Treatment results of 69 patients

We have studied the clinical courses of 69 patients with blastic crises of Philadelphia chromosome positive CML to identify parameters that were associated with an increased response rate or survival. Cytogenetic analysis at the time of blastic transformation revealed additional chromosome changes in 70% of the patients tested. Bone marrow fibrosis was detected in 58% of evaluable patients. Lymphoblastic transformation was seen in 28% of the patients tested with cell surface marker analysis. The value of 5'-nucleotidase as a marker for distinguishing lymphoid from non-lymphoid blast crisis was confirmed. Of 57 evaluable patients, 23 (40%) responded to therapy (CR/PR longer than 14 days). Median survival was 75 days. Longer survival was related to the following factors: Ph1-chromosome as the only detectable cytogenetic abnormality; lymphoblastic transformation; no bone marrow fibrosis; high percentage of blasts and promyelocytes in the bone marrow, and response to therapy. No prognostic significance was associated with age, sex, Tdt, LDH, spleen size, duration of the chronic phase of the disease, white blood cell count, Hb, platelet count and percentages of basophils, eosinophils, erythroblasts and blasts and promyelocytes in the peripheral blood. These data confirm the poor prognosis of patients with blastic crisis of CML treated by conventional chemotherapy.     

A new translocation involving three chromosomes in chronic myelocytic leukemia, 46,XY,t(9;11;22).

Bone-marrow metaphases in a 63-year-old male with newly discovered chronic myelocytic leukemia (CML) showed a complex translocation involving chromosomes 9, 11, and 22. About half of the short arm of chromosome 11 was translocated to the terminal part of the long arm of chromosome 9, and the missing fragment on chromosome 22 was translocated to the short arm of the abnormal chromosome 9. The clinical features were typical of CML, and the patient is in good physical condition 10 months after diagnosis on a regimen of busulfan.     

Novel variant Ph translocation t(9;22;11)(q34;q11.2;p15)inv(9)(p13q34) in chronic myeloid leukemia involving a one-step mechanism

Chronic myeloid leukemia (CML) is a clonal malignant disorder of a pluripotent hematopoietic stem cell characterized by the presence of a Philadelphia (Ph) chromosome. Less than 10% of patients present variant Ph chromosomes involving 1 or more additional chromosomes, other than chromosomes 9 and 22, with uncertain prognosis. There are mainly 1- or 2-step mechanisms proposed to explain the genesis of variant Ph chromosomes depending on whether the involved chromosomes are simultaneously broken and rejoined or if a standard t(9;22) occurs first. By combined standard cytogenetic and FISH analysis we detected a novel variant Ph translocation among chromosomes 9, 11 and 22 in a patient with CML without progression to an accelerated phase of the disease after 7 years, with the derivative chromosome 9 also having an acquired pericentric inversion. This novel case illustrates the use of FISH in metaphase to confirm a new rearrangement not previously described in variant Ph formation and that the present karyotype could have originated by a 1-step mechanism with 4 simultaneous breakages without deletion of ABL1.     

Patial trisomy 1 due to 1/17 translocation in Ph'-Positive chronic myelocytic leukemia

Summary A patient with chronic myelocytic leukaemia (CML) had the Philadelphia chromosome from the standard 9/22 translocation, a partial trisomy 1 secondary to an unbalanced 1/17 translocation, and a more recent clone with the addition of trisomy 22. This is the third case of partial trisomy 1 associated with the Philadelphia chromosome. Trisomy 1 in haematological disorders is discussed with reference to its clinical significance in CML, the segment of chromosome no. 1 involved, and the mechanisms of origin of the partial trisomies. Anomalies of chromosome 1, although not specific to any of them, seem to be important in the development of myeloproliferative disorders and of neoplasms in general.     

Asynchronous replication of p53 and 21q22 loci in chronic lymphocytic leukemia

In this study, in order to evaluate the replication pattern and the cell cycle dynamics of normal and malignant cells from patients with chronic lymphocytic leukemia, we applied the FISH technique with the p53 gene. Asynchrony was determined by the presence of one single and one set of double dots in the same cell. The rate of asynchronous replication was significantly higher in malignant cells than in normal cells (a mean of 28 vs 13, respectively, P = 0.023). There were proportionately more cells with two single dots among the normal cells (P = 0.0047). These results probably reflect the changes in gene replication and cell cycle progression that occur in malignant cells. Received: 25 March 1997 / Accepted: 28 July 1997     

A novel translocation,t(9;21)(q13;q22) rearranging the RUNX1 gene in acute myelomonocytic leukemia

A novel translocation t(9;21)(q13;q22) associated with trisomy 4 has been detected in a patient with acute myelomonocytic leukemia (AML,M4) in relapse. The chromosomal translocation results in rearrangement of the RUNX1 gene at 21q22. The DNA sequence rearranged on chromosome 9 remains unidentified. The diversity of the partners involved in translocations implicating RUNX1 suggests that the functional consequences of the abnormality are more due to the truncation of RUNX1 than to the identity of its partner in the rearrangement.     

C-abl and bcr are rearranged in a Ph1-negative CML patient.

Chromosomal analysis of a patient with chronic myelocytic leukemia (CML) revealed a translocation (9;12) (q34;q21) without a detectable Philadelphia chromosome (Ph1). Using molecular approaches we demonstrate (i) a rearrangement within the CML breakpoint cluster region (bcr) on chromosome 22, and (ii) a joint translocation of bcr and c-abl oncogene sequences to the derivative chromosome 12. These observations support the view that sequences residing on both chromosome 9 (c-abl) and 22 (bcr) are involved in the generation of CML and suggest that a subset of Ph1-negative patients may in fact belong to the clinical entity of Ph1-positive CML.     

Correlations between Ph 1 clone and leukocyte alkaline phosphatase on their associaton: chronic myeloid leukemia and pregnancy]

A biological [karyotype, leucocyte alkaline phosphatase (L.A.P.), haematimetry] and clinical study was performed on three women carriers of a chronic myaloid leukemia during their pregnancy (3 1/2 months, 6 1/2 months), or just after delivery. The results show : (1) a relation between the acuteness of the illness and a higher rate of L.A.P., probably secondary to pregnancy, and (2) a relation between the clinical evolution and the rate of Ph1 (+) cells.