TY - JOUR
T1 - Translocation of BCR to chromosome 9
T2 - A new cytogenetic variant detected by FISH in two Ph‐negative, BCR‐positive patients with chronic myeloid leukemia
AU - Hagemeijer, Anne
AU - Buijs, Arjan
AU - Smit, Elizabeth
AU - Janssen, Bart
AU - Creemers, Geert‐Jan ‐J
AU - Plas, Dorien Van Der
AU - Grosveld, Gerard
PY - 1993/1/1
Y1 - 1993/1/1
N2 - Leukemic cells from two patients with Philadelphia‐negative chronic myeloid leukemia (CML) were investigated: I) Cytogenetics showed a normal 46.XY karyotype in both cases, 2) molecular studies revealed rearrangement of the M‐BCR region and formation of BCR‐ABL fusion mRNA with b2a2 (patient I) or b3a2 (patient 2) configuration, and 3) fluorescence in situ hybridization (FISH) demonstrated relocation of the 5′ BCR sequences from one chromosome 22 to one chromosome 9. The ABL probe hybridized to both chromosomes 9 at band q34, while two other probes which map centromeric and telomeric of BCR on 22q 11 hybridized solely with chromosome 22. For the first time, a BCR‐ABL rearrangement is shown to take place on 9q34 instead of in the usual location on 22q 11. A rearrangement in the latter site is found in all Ph‐positive CML and in almost all investigated CML with variant Ph or Ph‐negative, BCR‐positive cases. The few aberrant chromosomal localizations of BCR‐ABL recombinant genes found previously were apparently the result of complex and successive changes. Furthermore in patient 2, both chromosomes 9 showed positive FISH signals with both ABL and BCR probes. Restriction fragment length polymorphism (RFLP) analysis indicated that mitotic recombination had occurred on the long arm of chromosome 9 and that the rearranged chromosome 9 was of paternal origin. The leukemic cells of this patient showed a duplication of the BCR‐ABL gene, analogous to duplication of the Ph chromosome in classic CML. In addition they had lost the maternal alleles of the 9q34 chromosomal region. The lymphocytes of patient 2 carried the maternal chromosome 9 alleles and were Ph‐negative as evidenced by RFLP and FISH analyses, respectively. © 1993 Wiley‐Liss, Inc.
AB - Leukemic cells from two patients with Philadelphia‐negative chronic myeloid leukemia (CML) were investigated: I) Cytogenetics showed a normal 46.XY karyotype in both cases, 2) molecular studies revealed rearrangement of the M‐BCR region and formation of BCR‐ABL fusion mRNA with b2a2 (patient I) or b3a2 (patient 2) configuration, and 3) fluorescence in situ hybridization (FISH) demonstrated relocation of the 5′ BCR sequences from one chromosome 22 to one chromosome 9. The ABL probe hybridized to both chromosomes 9 at band q34, while two other probes which map centromeric and telomeric of BCR on 22q 11 hybridized solely with chromosome 22. For the first time, a BCR‐ABL rearrangement is shown to take place on 9q34 instead of in the usual location on 22q 11. A rearrangement in the latter site is found in all Ph‐positive CML and in almost all investigated CML with variant Ph or Ph‐negative, BCR‐positive cases. The few aberrant chromosomal localizations of BCR‐ABL recombinant genes found previously were apparently the result of complex and successive changes. Furthermore in patient 2, both chromosomes 9 showed positive FISH signals with both ABL and BCR probes. Restriction fragment length polymorphism (RFLP) analysis indicated that mitotic recombination had occurred on the long arm of chromosome 9 and that the rearranged chromosome 9 was of paternal origin. The leukemic cells of this patient showed a duplication of the BCR‐ABL gene, analogous to duplication of the Ph chromosome in classic CML. In addition they had lost the maternal alleles of the 9q34 chromosomal region. The lymphocytes of patient 2 carried the maternal chromosome 9 alleles and were Ph‐negative as evidenced by RFLP and FISH analyses, respectively. © 1993 Wiley‐Liss, Inc.
UR - http://www.scopus.com/inward/record.url?scp=0027515807&partnerID=8YFLogxK
U2 - 10.1002/gcc.2870080406
DO - 10.1002/gcc.2870080406
M3 - Article
C2 - 7512367
AN - SCOPUS:0027515807
SN - 1045-2257
VL - 8
SP - 237
EP - 245
JO - Genes, Chromosomes and Cancer
JF - Genes, Chromosomes and Cancer
IS - 4
ER -