Determination of the frecuency of the fusion transcripts in bone marrow from patients with chronic myeloid leukemia (CML) and acute lymphoblawstic leukemia type B (B-ALL)

Authors

  • Oneida Morales Escuela de Química Biológica, Facultad de Ciencias Químicas y Farmacia.
  • Claudia Carranza
  • Patricia Saravia

Keywords:

BCL-ABL, RT.PCR, Choronic myeloid leukemia, type B acute lymphoblastic leukemia

Abstract

Determination of the frequency of the fusion transcripts in bone marrow from patients withchronic myeloid leukemia (CML) and acute lymphoblastic leukemia type B (B-ALL).

Abstract

At the molecular level translocation t(9;22) (q34, q11), known as the Philadelphia chromosome (Ph +),originates chimeric gene BCR-ABL coding for the expression of three fusion transcripts corresponding tob2a2, b3a2 and e1a2 . It has been shown that there is a relationship between the type of transcript pathologicaland clinical-demographic characteristics of leukemic patients. In Guatemala, there are no data regarding thefrequency of BCR-ABL transcripts in the diagnosis of leukemia, so now the genetic characterization of leukemicGuatemalan population with this condition has been impossible to make. The main objective of this studywas to determine the frequency of fusion transcripts BCR-ABL by means of the chain reaction technique ofreverse transcription polymerase (RT-PCR) in bone marrow samples from patients with CML and ALL-B tohelp the genetic characterization of leukemic Guatemalan population. In the present study we determined thatthe frequency of expression of different transcripts chimeric BCR-ABL gene in 35 bone marrow samples frompatients with CML and ALL-B corresponds to a low frequency for e1a2 transcript (11%) with respect to thefrequency of the b2a2 transcript (43%) and b3a2 (43%) and with a frequency of 3% coexpression representedby b2a2/b3a2 transcripts. Identified the predominance could e1a2 transcript in patients with ALL-B and b2a2and b3a2 transcripts and their coexpression (b2a2/b3a2) in CML patients, however no significant differencesin the frequency of expression of b2a2 and b3a2 compared (P= 0.369). It was found that the findings of studiesconducted in different geographical regions of the world for patients with ALL-B match with the frequencyreported in the Guatemalan in leukemic population with this condition detected in 100% of patients withtranscript expression pathological e1a2. We conclude that the frequency of BCR-ABL transcripts between theGuatemalan population CML agrees with that reported in studies conducted in Latin American countries,where the population is mainly mestizo group and is inverse to that reported in Western and Eastern countrieswhere there is predominance of Caucasian and Asian populations, because in such studies frequently reporteda significant difference between the expression frequency of b2a2 (30-40%) compared with b3a2 expression(50-60%). This suggests that the Guatemalan population expressing leukemic fusion transcripts of chimericBCR-ABL gene has a different biological behavior compared to that reported in Asian and Caucasian populationproduct of genetic variability among populations as a possible explanation for the differences observed in thisstudy.

Key words:

BCR-ABL, RT-PCR, Chronic myeloid leukemia, type B acute lymphoblastic leukemia

References

Referencias bibliográficas

Adler, R., Vielhmann, D., Kuhlisch, E., Martiniak, Y., Rottgers, S., Harbott, J. et al. (2009). Correlation of BCR-ABL transcript variants with patients characteristics in childhood chronic myeloid leukemia. European Journal of Haematology, 82, 112-118.

Almaguer, C. (2003). Interpretación clínica de la biometría hemática. Medicina Universitaria, 5, 35-40.

Arana, R., Sánchez, E., Ignacio, G., De La Fuente, E., Garces, O., Morales, E. et al. (2002). BCR-ABL p210, p190 and p230 fusion genes in 250 Mexican patients with chronic myeloid leukemia (CML). Clinical & Laboratory Haematology, 24, 145–150.

Aurer, I., Butturini, A., & Gale, R. (1991). BCR-ABL rearrangements in children with Philadelphia chromosome-positive chronic myelogenous leucemia. Blood, 78, 2407-10.

Balatzenko, G., Vundinti, B., & Guenova, M. (2001). Correlation between the type of BCR-ABL transcripts and blood cell counts in chronic myeloid leukemia: a possible influence of mdr1 gene expression. Hematology Reports, 3:e3, 5-8.

Benjamin, L., Ebert, A., & Todd, R. (2004). Genomic approaches to hematologic malignancies. Blood, 104, 923-932.

Bianchi, C., Cairoli, R., Marenco, P., Muti, G., Del Monte, U., & Perego, R. (1995). Detection by polymerase chain reaction of BCR-ABL transcripts in myeloproliferative diseases at time of diagnosis and for monitoring chronic myelogenous leukemia patients after bone marrow transplantation. European Journal of Cancer, 31A, 197– 201.

Branford, S., Hughes, T., & Rudzki, Z. (2002). Dual transcription of b2a2 and b3a2 BCR-ABL transcripts in chronic myeloid leukaemia is confined to patients with a linked polymorphism within the BCR gene. British Journal of Haematology, 117, 875-877.

Cerveira, N., Ferreira, S., Dória, S., Veiga, I., Ferreira, F., Mariz, J. et al. (2000). Detection of prognostic significant translocation in childhood acute lymphoblastic leukemia by one-step multiplex reverse transcription polymerase chain reaction, British Journal of Haematology, 109, 638-640.

Dobrovic, A., Trainor, K., & Morley, A. (1988). Detection of the molecular abnormality in chronic myeloid leukemia by use of the polymerase chain reaction. Blood, 72, 2063-2065.

de Klein, A., Van Kessel, A., Grosveld, G., Bartram C., Hagemeijer, A., Bootsma, D. et al. (1982). A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukemia. Nature, 300, 765-767.

de Lemos, J., de Oliveira, C., Scerni, A., Bentes, A. et al. (2005). Differential molecular response of the transcripts B2A2 and B3A2 to imatinib mesylate in chronic myeloid leukemia. Genetical Molecular Research, 4, 803-811.

Eisenberg, A., Silver, R., Soper, L., Arlin, Z., Coleman, M., Bernhardt, B. et al. (1988). The location of breakpoints within the breakpoint cluster region (bcr) of chromosome 22 in chronic myeloid leukemia. Leukemia, 2, 642-647.

Emad I., Osman, & Kamal, H. (2010). Frequencies of BCR-ABL fusion transcripts among Sudanese chronic myeloid leukemia patients. Genetics and Molecular Biology, 33, 229-231.

Fialkow, P., Jacobson, R., & Papayannopoulou, T. (1977). Chronic myelocytic leukemia: clonal origin a stem cell common to the granulocyte, erythrocyte, platelet and monocyte/macrophage. American Journal of Medicine, 63, 125-130.

Goh, H., Hwang, J., Kim, S., Lee, Y., Kim, Y, & Kim, D. (2006). Comprehensive analysis of BCR-ABL transcript types in Korean CML patients using a newly developed multiplex RT-PCR. Translational Research, 248, 249-56

Hasan, SK., Sazawal, S., Kumar, B., Chaubey, R., Mishra, P., Mir, R. et al. (2006). Childhood CML in India: b2a2 transcript is more common than b3a2. Cancer genetic Cytogenetic, 169, 76-7.

Heisterkamp, N., Stam, K., Groffen, J., de Klein, A., & Grosveld, G. (1985). Structural organization of the BCR gene and its role in the Ph translocation. Nature, 315, 758-761.

Henegariu, O., Heerema, N., Dlouhy, S., Vance, G., & Vogt, P. (1997). Multiplex PCR: critical parameters and step by step protocol. Biotechniques, 23, 504–511.

Hermans, A. Heisterkamp, N., von Lindern, M., van Baal, S., Meije, D., van der Plas, D. et al. (1987). Unique fusion of BCR and ABL genes in Philadelphia chromosome positive acute lymphoblastic leukemia. Cell, 51, 33-44.

Herrera, P., Calbacho, M., Heras, C., Ramos, M., López, J., & Odriozola, J. (2006). Monitorización de la enfermedad mínima residual en la leucemia mieloide crónica mediante la reacción en cadena de la polimerasa en tiempo real. Methods and Findings in Experimental & Clinical Pharmacology, 28, 47-54.

Ito, T., Tanaka, H., Tanaka, K., Ito, K., Kyo, T., Dohy, H. et al. (2004). Insertion of a genomic fragment of chromosome 19 between BCR intron 19 and ABL intron 1a in a chronic myeloid leukaemia patient with BCR-ABL (e19a2) transcript, British Journal of Haematology, 126, 750–5.

Lee, A., Kirk, J., Edmans, S., & Radich, J. (1995) Multiplex PCR of BCR/ABL fusion transcripts in Philadelphia positive acute lymphoblastic leukemia, Genome Research, 4, 283-287.

Lee, M., Le Maistre, A., Kantarjian, H., Talpaz, M., Freireich, E., Trujillo, J. et al. (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.

Lichty, B., Keating, A., Callum, J., Yee,K., Croxford, R.,Corpus, G. et al. (1998). Expression of p210 and p190 BCR-ABL due to alternative splicing in chronic myelogenous leukaemia. British Journal of Haematology, 103, 711-715.

Martiat, P., Ifrah, N., Rassool, F., Morgan, G. et al. (1989). Molecular analysis of Philadelphia positive essential thrombocythemia. Leukemia, 3,563-565.

Melo, J. (1996). The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype. Blood, 88, 2375.

Meza, J., Gutiérrez, M., Vásquez, A., Delgado, J., Esparza, M., Gonzáles, J. et al. (2007) Prevalence of the BCR-ABL1 transcripts in Mexican patients with chronic myelogenus leucemia. Review of Clinical Investigation, 59, 338-341.

Milis, K., Benn, P., & Birnie, G. (1991) Does the breakpoint within the major breakpoint cluster region (M-bcr) influence the duration of the chronic phase in chronic myeloid leukemia? An analytical comparison of current literature. Blood, 78, 1155-1161.

Millot, F., Traore, P., Guilhot, J., Nelken, B., Leblanc, T., Leverger, G. et al. (2005). Clinical and biological features at diagnosis in 40 children with chronic myeloid leukemia. Pediatrics, 116, 140-3.

Mondal, B., Bandyopadhyay, A., Majumdar, S., Mukhopadhyay, A., Chandra, S., Chaudhuri, U. et al. (2006). Molecular Profiling of Chronic Myeloid Leukemia in Eastern India, American Journal of Hematology, 81, 845–849

Nowell, P., & Hungerford, D. (1960) A minute chromosome in human chronic granulocytic leukemia. Science, 132, 1497.

Olopade, I., & Pichert G. (2001). Cancer genetics in oncology practice. Annals of Oncology, 12, 895-908.

Opalka, B., Wandl, U., Stutenkemper, R., Kloke, O. et al. (1992). No correlation between the type of Bcr-Abl hybrid messenger RNA and platelet counts in chronic myelogenous leukemia. Blood, 80, 1854-1855.

Paz, C., Burgo, R., Morillo, S., Santos, J., Fiallo, B., & Leone, P. (2002). BCR-ABL rearrangement frequencies in chronic myeloid leukemia and acute lymphoblastic leukemia in Ecuador, South America. Cancer Genetics & Cytogenetics, 132, 65-67.

Perego, R., Costantini, M., Cornacchini, G., Gargantini, L., Bianchi, C., Pungolino, E. et al. (2000). The possible influences of b2a2 and b3a2 BCR-ABL protein structure on thrombopoiesis in chronic myeloid leukemia. European Journal of Cancer, 36, 1395–1401.

Rosas, A., Martinez, M., Ayala, M., Vela, J., Bahena, P., Vadillo, M. et al. (2003). Análisis del tipo de transcrito BCR-ABL y su relación con la cuenta plaquetaria en pacientes mexicanos con leucemia mieloide crónica. Gaceta Médica de México, 139, 553-559.

Rozman, C., Urbano, A., Cervantes, F., Rozman, M., Colomer, D., Féliz, P. et al. (1995). Analysis of the clinical relevance of the breakpoint location within M-bcr and the type of chimeric mRNA in chronic myelogenous leukemia. Leukemia, 9, 1104-1107.

Ruiz, G., Garcés, J., Reyes, V., & Ruiz, G. (2004). Frequencies of the breakpoint cluster region types of the BCR-ABL fusion gene in Mexican Mestizo patients with chronic myelogenous leukemia. Journal of Clinical Research, 56, 605-8

Shepherd, P., Bond, C., & Allan, N. (1992). Molecular breakpoints and platelet counts in chronic myeloid leukemia. Blood, 80, 556-557.

Shepherd, P., Suffolk, R., Halsey, J., & Allan, N. (1995). Analysis of molecular breakpoint and m-RNA transcript in a prospective randomized trial of interferon in chronic mueloid leukaemia: no correlation with clinical features, cytogenetic response, duration of chronic phase, or survival, British Journal of Haematology, 89, 546-54.

Udomsakdi-Auewarakul, C., U-Pratya, Y., Boonmoh, S., & Vatanavicharn, S. (2000). Detection of molecular variants of BCR-ABL gene in bone marrow and blood of patients with chronic myeloid leukemia by reverse-transcriptase polymerase chain reaction (RT-PCR). Journal of the Medicine Association of Thailand, 83, 928 –35.

van Rhee, F., Hochhaus, A., Lin, F., Melo, J., Goldman, J., & Cross, N. (1996) p190 BCR-ABL mRNA is expressed at low levels in p210-positive chronic myeloid and acute lymphoblastic leukemias. Blood, 87, 5213–5217.

Yaghmaie, M., Ghaffari, S., Ghavamzadeh, A., Alimoghaddam, K., Jahani, M., Mousavi, S. et al. (2008). Frequency of BCR-ABL Fusion Transcripts in Iranian Patients with Chronic Myeloid Leukemia. Iranian Archive of Medicine, 11, 247 – 251

Downloads

Published

2012-11-19

Issue

Section

Artículos