Summary
We investigated the breakpoints of thebcr gene in 46 Ph1-positive CML cases by Southern blot analysis ofbcr rearrangement, and in 17 CML cases by a combination of Southern blot analysis and RT-PCR. By Southern blot, the breakpoint was not identified on M-bcr in three CML cases, of which one case showed the P210-typebcr/abl transcript and two cases showed the ALL-type (P190-type)bcr/abl transcript with or without P210 transcript. Later two cases showed unique hematological profiles such as thrombocytosis, mild myelofibrosis, and relative resistance to alkylating agents. Therefore, the present study suggests that expression of the P190-type transcript may affect clinical and hematological findings in CML.
Similar content being viewed by others
References
Bartram CR, Bross-Bach U, Schmidt H, Waller HD (1987) Philadelphia-positive chronic myelogenous leukemia with breakpoint 5′ of the breakpoint cluster region but within the bcr gene. Blut 55:505–511
Berger R, Chen SJ, Chen Z (1990) Philadelphia-positive acute leukemia; cytogenetic and molecular aspects. Cancer Genet Cytogenet 44:143–152
Chan LC, Karhi KK, Rayter SI, Heisterkamp N, Eridani S, Powles R, Lawler SD, Groffen J, Foulkes JG, Greaves MF, Wiedeman LM (1987) A novel abl protein expressed in Philadelphia chromosome-positive acute lymphoblastic leukemia. Nature 325:635–637
Chen SJ, Chen Z, Grausz D, Hillion J, d'Auriol L, Flandrin G, Larsen CJ, Berger R (1988) Molecular cloning of a 5′ segment of the genomic Ph1 gene defines a new breakpoint cluster region (bcr2) in Philadelphia-positive acute leukemia. Leukemia 2:634–641
Chen SJ, Chen Z, Hillion J, Grausz D, Loiseau P, Flandrin G, Berger R (1989) Ph1-positive, bcr-negative acute leukemias: clustering of breakpoints chromosome 22 in the 3′ end of the bcr gene first intron. Blood 73:1312–1315
Dhingra K, Talpaz M, Kantarjian H, Ku S, Rothberg J, Gutterman JU, Kurzrock R (1991) Appearance of acute leukemia-associated P190BCR-ABL in chronic myelogenous leukemia may correlate with disease progression. 5:191–195
Dobrovic A, Trainor KJ, Morley AA (1988) Detection of the molecular abnormality in chronic myeloid leukemia by use of the polymerase chain reaction. Blood 72:2063–2065
Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G (1984) Philadelphia chromosome breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell 36:93–99
Guo JQ, Hirsch Ginsberg CF, Xian YM, Stass SA, Champlin RE, Gilart SA, McCredie KB, Campbell ML, Arlinghaus RB (1993) Acute lymphoid leukemia molecular phenotype in patient with benign-phase chronic myelogenous leukemia. Hematol Pathol 7:91–106
Heisterkamp N, Stephenson JR, Groffen J, Hansen PF, de Klein A, Bartram CR, Grosveld G (1983) Localization of the c-abl oncogene adjustment to a translocation breakpoint in chronic myelocytic leukemia. Nature 306:239–242
Hermans A, Heisterkamp N, van Lindern M, van Baal S, Meijer D, van der Plas D, Wiedeman LM, Groffen J, Bootsma D, Grosveld G (1987) Unique fusion of bcr and c-abl genes in Philadelphia chromosome-positive acute lymphoblastic leukemia. Cell 51:33–40
Konopka JB, Witte ON (1985) Detection of c-abl tyrosine kinase activity in vitro permits direct comparison of normal and altered abl gene products. Mol Cell Biol 5:3116–3123
Kwok S, Higuchi R 1989) Avoiding false positives with PCR. Nature 339:237
Lee MS, LeMaistre A, Kantajian HM, Talpaz M, Freireich EJ, Trujillo JM, Stass SA (1989) Detection of two alternative bcr-abl mRNA junctions and minimal residual disease in Philadelphia chromosome-positive chronic myelogenous leukemia by polymerase chain reaction. Blood 73:2165–2170
Lozzio CB, Lozzio BB (1975) Human chronic myelogenous leukemia cell line with positive Philadelphia chromosome. Blood 45:321–334
Melo JV, Myint H, Galton DA, Goldman JM (1994) P190BCR-ABL chronic myeloid leukaemia: the missing link with chronic myelomonocytic leukaemia? Leukemia 8:208–211
Nakamura Y, Hirosawa S, Aoki N (1993) Consistent involvement of the 3′ half part of the first BCR intron in adult Philadelphia-positive leukaemia without M-bcr rearrangement. Br J Haematol 83:53–57
Nowell PC, Hungerford DA (1960) A minute chromosome in human chronic granulocytic leukemia. Science 132:1497
Okabe M, Kunieda Y, Saiki I, Sikano T, Kakinuma M, Miyazaki T (1990) Blast crisis accompanied with occurrence of the point-mutational activation of N-ras proto-oncogene and chromosomal abnormality inv(3q) in chronic myelogenous leukemia presenting thrombocytosis. Leukemia 4:381–382
Okabe M, Kunieda Y, Sugiura T, Tanaka M, Miyagishima T, Saiki I, Minagawa T, Kurosawa M, Itaya T, Miyazaki T (1991) Inhibitory effect of interleukin-4 on the in vitro growth of Ph1-positive acute lymphoblastic leukemia cells. Blood 78:1574–1580
Okabe M, Matsushima S, Morioka M, Kobayashi M, Abe S, Sakurada K, Kakinuma M, Miyazaki T (1987) Establishment and characterization of cell line, TOM-1, derived from a patient with Philadelphia chromosome-positive acute lymphocytic leukemia. Blood 69:990–998
Okabe M, Oita M, Kunieda Y, Matuura J, Sakurada K, Matsushima S, Kakinuma M, Miyazaki T (1989) Bcr rearrangement and c-abl gene expression on Phi-positive hybrid acute leukemia with simultaneous proliferation of lymphoid and myeloid blasts. Blut 58:241–246
Popenoe DW, Schaefer-Rego K, Mears JG, Bank A, Leibowitz D (1986) Frequent and extensive deletion during the 9, 22 translocation in CML. Blood 68:1123–1128
Rowley JD (1973) A new consistent chromosomal abnormality in chronic myelogenous leukemia identified by quinacrine fluorescence and Giemsa staining. Nature 243:290–293
Sawyers CL, Timson L, Kawasaki ES, Clark SS, Witte ON, Champlin R (1990) Molecular relapse in chronic myelogenous leukemia patients after bone marrow transplantation detected by polymerase chain reaction. Proc Natl Acad Sci USA 87:563–567
Selleri L, Narni F, Emilia G, Colo A, Zucchini P, Venturelli D, Donelli A, Torelli U, Torelli G (1987) Philadelphia-positive chronic myeloid leukemia with a chromosome 22 breakpoint outside the breakpoint cluster region. Blood 70:1659–1664
Selleri L, von Lindern M, Hermans A, Meijer D, Torelli G, Grosveld G (1990) Chronic myeloid leukemia may be associated with several bcr-abl transcripts including the acute lymphoid leukemia-type 7 kb transcript. Blood 75:1146–1153
Stivelman E, Lifshitz B, Gale RP, Roe BA, Canaani E (1985) Fused transcript of abl and bcr genes in chronic myelogenous leukemia. Nature 315:550–554
Zaccaria A, Tassinari A, Testoni N, Lauria F, Tura S, Algeri R, Guerrasio A, Rosso C, Saglio G (1990) Alternative BCR/ABL transcripts in chronic myeloid leukemia. Blood 76:1663–1665
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kunieda, Y., Okabe, M., Kurosawa, M. et al. Chronic myeloid leukemia presenting ALL-type BCR/ABL transcript. Ann Hematol 69, 189–193 (1994). https://doi.org/10.1007/BF02215952
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02215952