BCR/ABL fusion located on chromosome 9 in chronic myeloid leukemia with a masked Ph chromosome
Corresponding Author
Anwar N. Mohamed MD
Cytogenetics Laboratory, Departments of Pathology and Internal Medicine/Harper Hospital, Wayne State University, Detroit, Michigan
Pathology Department/Cytogenetics, Wayne State University/Harper Hospital, 3990 John R, Detroit, MI 48201, U.S.A.Search for more papers by this authorF. Koppitch
Cytogenetics Laboratory, Departments of Pathology and Internal Medicine/Harper Hospital, Wayne State University, Detroit, Michigan
Search for more papers by this authorM. Varterasian
Cytogenetics Laboratory, Departments of Pathology and Internal Medicine/Harper Hospital, Wayne State University, Detroit, Michigan
Search for more papers by this authorC. Karanes
Cytogenetics Laboratory, Departments of Pathology and Internal Medicine/Harper Hospital, Wayne State University, Detroit, Michigan
Search for more papers by this authorKai-Ling Yao
Cytogenetics Laboratory, Departments of Pathology and Internal Medicine/Harper Hospital, Wayne State University, Detroit, Michigan
Search for more papers by this authorF. H. Sarkar
Cytogenetics Laboratory, Departments of Pathology and Internal Medicine/Harper Hospital, Wayne State University, Detroit, Michigan
Search for more papers by this authorCorresponding Author
Anwar N. Mohamed MD
Cytogenetics Laboratory, Departments of Pathology and Internal Medicine/Harper Hospital, Wayne State University, Detroit, Michigan
Pathology Department/Cytogenetics, Wayne State University/Harper Hospital, 3990 John R, Detroit, MI 48201, U.S.A.Search for more papers by this authorF. Koppitch
Cytogenetics Laboratory, Departments of Pathology and Internal Medicine/Harper Hospital, Wayne State University, Detroit, Michigan
Search for more papers by this authorM. Varterasian
Cytogenetics Laboratory, Departments of Pathology and Internal Medicine/Harper Hospital, Wayne State University, Detroit, Michigan
Search for more papers by this authorC. Karanes
Cytogenetics Laboratory, Departments of Pathology and Internal Medicine/Harper Hospital, Wayne State University, Detroit, Michigan
Search for more papers by this authorKai-Ling Yao
Cytogenetics Laboratory, Departments of Pathology and Internal Medicine/Harper Hospital, Wayne State University, Detroit, Michigan
Search for more papers by this authorF. H. Sarkar
Cytogenetics Laboratory, Departments of Pathology and Internal Medicine/Harper Hospital, Wayne State University, Detroit, Michigan
Search for more papers by this authorAbstract
A reciprocal translocation, t(10; 22) (q22; q11), resulting in a masked Ph chromosome was identified in a patient diagnosed with chronic myeloid leukemia (CML). Both homologs of chromosome 9 were of the normal pattern. Two signals for the ABL probe, both of them hybridized to chromosome 9, were demonstrated via fluorescence in situ hybridization (FISH). Furthermore, cohybridization with two differently labeled BCR/ABL translocation DNA probes indicated a BCR/ABL fusion apparently located on 9q34. Molecular studies revealed a rearrangement of the BCR region and expression of a chimeric BCR/ABL mRNA of CML configuration. These findings indicate that the BCR/ABL fusion resulted from an unusual relocation of the BCR gene from its normal position on 22ql I to 9q34 adjacent to the ABL gene.
References
- Arnoldus EPJ, Wiegant J, Noordermeer IA, Wessels JW, Beverstock GC, Grosveld GC, van der Ploeg M, Raap AK (1990) Detection of the Philadelphia chromosome in interphase nuclei. Cytogenet Cell Genet 54: 108–111.
- Bentz M, Cabot G, Moos M, Speicher MR, Ganser A, Lichter P, Dohner H (1994) Detection of chimeric BCR-ABL genes on bone marrow samples and blood smears in chronic myeloid and acute lymphoblastic leukemia by in situ hybridization. Blood 83: 1922–1928.
- De Klein A, Geurts van Kessel A, Grosveld G, Bartram CR, Hagemeijer A, Bootsma D, Spurr NK, Heisterkamp N, Groffen J, Stephenson JR (1982) A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukemia. Nature 300: 765–767.
- Dube I, Dixon J, Beckett T, Grossman A, Weinstein M, Benn P, McKeithan T, Norman C, Pinkerton P (1989) Location of breakpoints within the major breakpoint cluster region (BCR) in 33 patients with bcr-rearrangement-positive chronic myeloid leukemia (CML) with complex or absent Philadelphia chromosomes. Genes Chromosom Cancer 1: 106–111.
- Eisenberg A, Silver R, Soper L, Arlin Z, Coleman M, Bernhardt B, Benn P (1988) The location of breakpoints within the breakpoint cluster region (bcr) of chromosome 22 in chronic myeloid leukemia. Leukemia 2: 642–647.
- Hagemeijer A, de Klein A, Godde-Salz E, Turc-Carel C, Smit EME, van Agthoven AJ, Grosveld GC (1985) Translocation of c-abl to masked Ph in chronic myeloid leukemia. Cancer Genet Cytogenet 18: 95–104.
- Hagemeijer A, Buijs A, Smit E, Janssen B, Creemers GJ, Van der Plas D, Grosveld G (1993) Translocation of BCR to chromosome 9: A new cytogenetic variant detected by FISH in two Ph-negative, bcr-positive patients with chronic myeloid leukemia. Genes Chromosom Cancer 8: 237–245.
- Heim S, Billstrom R, Kristofferson U, Mandahl N, Strombeck B, Mitelman F (1985) Variant Ph translocations in chronic myeloid leukaemia. Cancer Genet Cytogenet 18: 215–227.
- Heisterkamp N, Stephenson JR, Groffen J, Hansen PF, de Klein A, Bartram CR, Grosveld G (1983) Localization of the c-abl oncogene adjacent to a translocation breakpoint in chronic myelocytic leukemia. Nature 306: 239–242.
- Kawasaki ES, Clark SS, Coyne MY, Smith SD, Champlin R, Witte ON, McCormick FP (1988) Diagnosis of chronic myeloid and acute lymphocytic leukemias by detection of leukemia-specific mRNA sequences amplified in vitro. Proc Natl Acad Sci USA 85: 5698–5702.
- Mohamed AN, Clarkson BD, Chaganti RSK (1986) High resolutionbanding of chronic myeloid leukemia chromosomes. Cancer Genet Cytogenet 20: 209–222.
- Morris CM, Fitzgerald PH (1987) Complexity of an apparently simple Ph translocation in CML. Leukemia Res 11: 163–169.
- Morris CM, Rosman I, Archer SA, Cochrane JM, Fitzgerald PH (1988) A cytogenetic and molecular analysis of five variant Philadelphia translocations in chronic myeloid leukemia. Cancer Genet Cytogenet 35: 179–197.
- Morris CM, Kennedy M, Heisterkamp N, Columbano-Green L, Remeril K, Groffen J, Fitzgerald P (1991) A complex chromosome rearrangement forms the BCR-ABL fusion gene in leukemic cells with a normal karyotype. Genes Chromosom Cancer 3: 263–271.
- Nacheva E, Holloway T, Brown K, Bloxham D, Green AR (1994) Philadelphia-negative chronic myeloid leukemia: Detection by FISH of BCR-ABL fusion gene localized either to chromosome 9 or chromosome 22. Br J Haematol 87: 409–411.
- Ohyashiki K, Ohyashiki JH, Otaki K, Yoshida MA, Ram A, Preisler HD, Sandberg AA (1987) Four cases with complex Philadelphia translocations, including one with appearance de novo of a “masked” Ph. Cancer Genet Cytogenet 24: 281–294.
- Rowley JD (1973) A new consistent chromosomal abnormality in chronic myelogenous leukemia identified by quinacrine fluorescence and Giemsa staining. Nature 243: 290–293.
- J Sambrook, EF Fritsch, T Maniatis (eds; 1989): Molecular Cloning, A Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press.
- Sarkar FH, Li YW, Ball DE, Crissman JD (1992) A comparative method for the detection of RNA-PCR amplified signals. Biotechniques 12: 22–26.
- Shtivelman E, Lifshitz B, Gale RP, Canaani E (1985) Fused transcript of abl and bcr genes in chronic myelogenous leukemia. Nature 315: 550–555.
- Tkachuk DC, Westbrook CA, Andreef M, Donlon TA, Cleary ML, Suryanarayan K, Homge M, Redner A, Gray J, Pinkel D (1990) Detection of bcr-abl fusion in chronic myelogenous leukemia by in situ hybridization. Science 250: 559–561.
- Van der Plas DC, Ilermans ABC, Soekarman D, Smit EME, de Klein A, Smadja N, Aljmena G, Goudsmit R, Grosveld G, Hagemeijer A (1989) Cytogenetic and molecular analysis in Philadelphia negative CML. Blood 73: 1038–1044.