Distribution of breakpoint within the breakpoint cluster region (bcr) in chronic myelogenous leukemia with a complex philadelphia chromosome translocation

We analyzed, by Southern blot hybridization, the site of breakpoint within the breakpoint cluster region (bcr) in six patients with a complex Philadelphia chromosome (Ph) translocation and in 23 unselected patients with a standard Ph. The breakpoint was found within the 5.8 kb bcr in all 29 patients. When the bcr was subdivided into four parts, fragments I–IV, based on the restriction enzyme sites, among the six patients with a complex Ph, two had a breakpoint at fragment I, three at fragment II, and one at fragment III. This distribution of breakpoints in patients with a complex Ph did not differ significantly from that in patients with a standard Ph. A deletion of an allele within the bcr was found in three patients (50%) with a complex Ph and in three (13%) with a standard Ph. The internal bcr deletion may be more common in patients with a complex Ph.

[1]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[2]  J. Inazawa,et al.  DNA analysis using long-term preserved fixed cytogenetic preparations , 1988, Japanese Journal of Human Genetics.

[3]  C. Morris,et al.  A cytogenetic and molecular analysis of five variant Philadelphia translocations in chronic myeloid leukemia. , 1988, Cancer genetics and cytogenetics.

[4]  R. Silver,et al.  The location of breakpoints within the breakpoint cluster region (bcr) of chromosome 22 in chronic myeloid leukemia. , 1988, Leukemia.

[5]  K. Mills,et al.  The site of the breakpoint within the bcr is a prognostic factor in Philadelphia-positive CML patients. , 1988, Blood.

[6]  R. Kurzrock,et al.  Analysis of breakpoints within the bcr gene and their correlation with the clinical course of Philadelphia-positive chronic myelogenous leukemia. , 1988, Blood.

[7]  M. Shibuya,et al.  Undetectable bcr‐abl rearrangements in some CML patients are due to a deletion mutation in the bcr gene , 1988, American journal of hematology.

[8]  M. Minamihisamatsu,et al.  The Philadelphia chromosome. Considerations based on studies of variant Ph translocations. , 1988, Cancer genetics and cytogenetics.

[9]  J. Mears,et al.  CML patients in blast crisis have breakpoints localized to a specific region of the BCR , 1987 .

[10]  G. Torelli,et al.  Molecular study of the Philadelphia translocation in chronic myelogenous leukemia in different stages of disease. , 1987, Haematologica.

[11]  J. Mears,et al.  Frequent and extensive deletion during the 9,22 translocation in CML. , 1986, Blood.

[12]  H. Ijichi,et al.  Inversion of chromosome 3 in a case of chronic myelogenous leukemia with abnormal thrombopoiesis. , 1986, Cancer genetics and cytogenetics.

[13]  E. Canaani,et al.  Fused transcript of abl and bcr genes in chronic myelogenous leukaemia , 1985, Nature.

[14]  Kees Stam,et al.  Structural organization of the bcr gene and its role in the Ph′ translocation , 1985, Nature.

[15]  N. Heisterkamp,et al.  C‐abl and bcr are rearranged in a Ph1‐negative CML patient. , 1985, The EMBO journal.

[16]  R. Kurzrock,et al.  The human cellular abl gene product in the chronic myelogenous leukemia cell line K562 has an associated tyrosine protein kinase activity. , 1985, Virology.

[17]  B. Mendelow,et al.  The incidence, type, and subsequent evolution of 14 variant Ph1 translocations in 180 South African patients with Ph1-positive chronic myeloid leukemia. , 1984, Cancer genetics and cytogenetics.

[18]  Susan M. Watanabe,et al.  An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity , 1984, Cell.

[19]  J. Stephenson,et al.  Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22 , 1984, Cell.

[20]  A. Sandberg.  Chromosomes and causation of human cancer and leukemia: XL. The Ph1 and other translocations in CML , 1980, Cancer.

[21]  E. Southern.  Detection of specific sequences among DNA fragments separated by gel electrophoresis. , 1975, Journal of molecular biology.

[22]  S. Misawa,et al.  A five-way complex translocation in a patient with chronic myelocytic leukemia: t(4;18;13;9;22)(q12;q11.2;q14;q34;q11.2). , 1988, Cancer Genetics and Cytogenetics.

[23]  M. Braekeleer.  Variant Philadelphia translocations in chronic myeloid leukemia. , 1987 .

[24]  Iscn.  International System for Human Cytogenetic Nomenclature , 1978 .