Biopolym. Cell. 2000; 16(6):482-486.
http://dx.doi.org/10.7124/bc.00058D
Structure and Function of Biopolymers
Mutation in bcr/abl hybrid gene as a possible factor of tumor progression during CML
1Telegeev G. D., 1Dubrovska A. N., 1Dybkov M. V., 1Maliuta S. S.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680

Abstract

The bcr/abl hybrid gene is a hallmark of CML and of many cases of acute leukemias (ALL). The expression of this gene is the condition of the beginning or one of the stages of these diseases. In contrast to ALL, the bcr/abl fusion gene in CML has additional 3–10 exons (Dbl and PH domains). We analyzed this region seeking a cause of the blast crisis. The sequencing of RT/PCR product has revealed the point mutation at nucleotide 2109 of bcr/abl mRNA (the transition mutation from T to C) causing the amino acid change from Phe547 to Leu547. Using FITC-phalloidin we have shown the paramembrane actin location.
Full text: (PDF, in Ukrainian)

References

[1] Nowell PC, Hungerpord DA. A minute chromosome in human chronic granulocytic leukemia. Science. 1960; 132:1497-9.
[2] Maurer J, Janssen JW, Thiel E, van Denderen J, Ludwig WD, Aydemir U, Heinze B, Fonatsch C, Harbott J, Reiter A, et al. Detection of chimeric BCR-ABL genes in acute lymphoblastic leukaemia by the polymerase chain reaction. Lancet. 1991;337(8749):1055-8.
[3] Melo JV. The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype. Blood. 1996;88(7):2375-84.
[4] Martiat P, Mecucci C, Nizet Y, Stul M, Philippe M, Cassiman JJ, Michaux JL, Van den Berghe H, Sokal G. P190 BCR/ABL transcript in a case of Philadelphia-positive multiple myeloma. Leukemia. 1990;4(11):751-4.
[5] Mitani K, Sato Y, Tojo A, Ishikawa F, Kobayashi Y, Miura Y, Miyazono K, Urabe A, Takaku F. Philadelphia chromosome positive B-cell type malignant lymphoma expressing an aberrant 190 kDa bcr-abl protein. Br J Haematol. 1990;76(2):221-5.
[6] Teleheiev HD, Dybkov MV, Bozhko MV, Tretiak NM, Maliuta SS. The molecular biology diagnosis of neoplastic blood diseases. Tsitol Genet. 1998;32(1):71-8.
[7] Pane F, Frigeri F, Sindona M, Luciano L, Ferrara F, Cimino R, Meloni G, Saglio G, Salvatore F, Rotoli B. Neutrophilic-chronic myeloid leukemia: a distinct disease with a specific molecular marker (BCR/ABL with C3/A2 junction). Blood. 1996;88(7):2410-4. Erratum in: Blood 1997 Jun 1;89(11):4244.
[8] Ahmed S, Lee J, Wen LP, Zhao Z, Ho J, Best A, Kozma R, Lim L. Breakpoint cluster region gene product-related domain of n-chimaerin. Discrimination between Rac-binding and GTPase-activating residues by mutational analysis. J Biol Chem. 1994;269(26):17642-8.
[9] Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987;162(1):156-9.
[10] Telegeev GD, Dybkov MV, Bozhko MV, Tretiak NM, Maliuta SS. Molecular-biology approaches to detection of Philadelphia chromosome in patients with leukemia. Biopolym Cell. 1996; 12(6):63-8.
[11] Maniatis T, Fritsch EF, Sambrook J. Molecular cloning: a laboratory manual. New York: Cold Spring Harbor Lab, 1982; 545 p.
[12] Mandel M, Higa A. Calcium-dependent bacteriophage DNA infection. J Mol Biol. 1970;53(1):159-62.
[13] Birnboim HC, Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979;7(6):1513-23.
[14] McWhirter JR, Wang JY. Activation of tyrosinase kinase and microfilament-binding functions of c-abl by bcr sequences in bcr/abl fusion proteins. Mol Cell Biol. 1991;11(3):1553-65.
[15] Miki T, Smith CL, Long JE, Eva A, Fleming TP. Oncogene ect2 is related to regulators of small GTP-binding proteins. Nature. 1993;362(6419):462-5.
[16] Ridley AJ, Hall A. The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell. 1992;70(3):389-99.
[17] Matsuguchi T, Inhorn RC, Carlesso N, Xu G, Druker B, Griffin JD. Tyrosine phosphorylation of p95Vav in myeloid cells is regulated by GM-CSF, IL-3 and steel factor and is constitutively increased by p210BCR/ABL. EMBO J. 1995;14(2):257-65.
[18] Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell. 1992;70(3):401-10.
[19] Crespo P, Bustelo XR, Aaronson DS, Coso OA, Lopez-Barahona M, Barbacid M, Gutkind JS. Rac-1 dependent stimulation of the JNK/SAPK signaling pathway by Vav. Oncogene. 1996;13(3):455-60.
[20] McWhirter JR, Wang JY. An actin-binding function contributes to transformation by the Bcr-Abl oncoprotein of Philadelphia chromosome-positive human leukemias. EMBO J. 1993;12(4):1533-46.
[21] Van Etten RA, Jackson PK, Baltimore D, Sanders MC, Matsudaira PT, Janmey PA. The COOH terminus of the c-Abl tyrosine kinase contains distinct F- and G-actin binding domains with bundling activity. J Cell Biol. 1994;124(3):325-40.
[22] Hall A. Rho GTPases and the actin cytoskeleton. Science. 1998;279(5350):509-14.
[23] Van Aelst L, D'Souza-Schorey C. Rho GTPases and signaling networks. Genes Dev. 1997;11(18):2295-322.