Share This Article:

Applications of Fluorescence in Situ Hybridization (FISH) for Detecting Genetic Changes in Hematological Malignancies

Abstract Full-Text HTML Download Download as PDF (Size:328KB) PP. 125-134
DOI: 10.4236/jct.2011.22014    6,705 Downloads   11,972 Views   Citations


Fluorescence in situ hybridization (FISH) has become an important tool both for defining initial chromosomal abnormalities within a disease process, and for monitoring response to therapy as well as minimal residual disease. We report the results of interphase FISH (iFISH) analysis of 92 patients. We have used five different FISH probes to detect common cytogenetic rearrangements associated with hematological malignancies. A total of 83 patients were screened for BCR/ABL gene rearrangements. Displayed iFISH patterns of BCR/ABL gene rearrangements in 37.3% of patients (31/83) ranged between 10% to 98%. In addition, while 3 patients and one patient with AML showed t(15; 17) (12.5%) and inv(16; 16) (8.3%) respectively, t(8; 21) was not found. Furthermore, secondary chromosomal aberrations (6.5% of all cases) were clearly non random in the present study. The diagnosis of BCR/ABL gene rearrangements are likely become an important tool for the monitoring of therapies in patients with CML. Atypical patterns also may have clinical prognostic implications. Further studies in larger groups of patients are needed in order to elucidate the role of AML1/ETO, PML/RARA, CBFB and p53, and to identify the specific chromosomal regions and interacting genes involved in this process.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

D. Taştemir, O. Demirhan, E. Gürkan, E. Tunç and N. İnandıklıoğlu, "Applications of Fluorescence in Situ Hybridization (FISH) for Detecting Genetic Changes in Hematological Malignancies," Journal of Cancer Therapy, Vol. 2 No. 2, 2011, pp. 125-134. doi: 10.4236/jct.2011.22014.


[1] E. S. Jaffe, N. L. Harris, H. Stein and J. W. Vardiman, “World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues,” IARC Press, Lyon, 2001.
[2] F. Mitelman, B. Johansson and F. Mertens, “The ?mpact of Translocations and Gene Fusions on Cancer Causation,” Nature Reviews Cancer, Vol. 7, No. 4, 2007, pp. 233-245. doi:10.1038/nrc2091
[3] J. D. Rowley, “Chromosomal Translocations: Revisited yet Again”, Blood, Vol. 112, No. 6, 2008, p. 2183. doi:10.1182/blood-2008-04-097931
[4] B. Mohr, M. Bornhauser, U. Platzbecker, J. Freiberg- Richter, R. Naumann, G. Prange-Krex, J. Mohm, F. Kroschinsky, G. Ehninger and C. Thiede, “Problems with ?nterphase Fluorescence in Situ Hybridization in Detec- ting BCRABL Positive Cells in Some Patients Using a Novel Technique with Extra Signals,” Cancer Genet Cytogenet, Vol. 127, No. 2, 2001, pp. 111-117.doi:10.1016/S0165-4608(00)00371-X
[5] G. W. Dewald, T. C. Smyrk, E. C. Thorland, R. R. McWilliams, D. L. van Dyke, J. G. Kefe, K. J. Belongie, S. A. Smoley, D. L. Knutson, S. R. Fink, A. E. Wiktor and G. M. Petersen, “Fluorescence in Situ Hybridization to Visualize Genetic Abnormalities in Interphase Cells of Acinar Cell Carcinoma, Ductal Adenocarcinoma, and Islet Cell Carcinoma of the Pancreas,” Mayo Clinic Proceedings, Vol. 84, No. 9, 2009, pp. 801-810. doi:10.4065/84.9.801
[6] W. G. Finn and L. C. Peterson, “Hematopathology in Oncology,” Kluwer Academic Publishers, New York, 2004. doi:10.1007/b113185
[7] A. Hagemeijer, A. Buijs, E. Smit, B. Janssen, G. J. Creemers, D. van der Plas and G. Grosveld, “Trans- location of BCR to Chromosome 9: A New Cytogenetic Variant Detected by FISH in Two Ph-Negative, BCR-Positive Patients with Chronic Myeloid Leukemia,” Genes, Chromosomes and Cancer, Vol. 8, No. 4, 1993, pp. 237-245. doi:10.1002/gcc.2870080406
[8] M. J. Macera, L. J. Smith, E. Frankel, P. Szabo and R. S. Verma, “A Philadelphia Negative Chronic Myelogenous Leukemia with the Chimeric BCR/ABL Gene on Chromo- some 9 and a B3-A2 Splice Junction,” Cancer, Genetics and Cytogenetics, Vol. 101, 1998, pp. 143-147.doi:10.1016/S0165-4608(97)00257-4
[9] W. T. Hsu, H. Preisler, K. Szego, R. Sprudzs and X. Z. Gao, “The ABL/BCR Fusion Gene on Chromosome 9 in Ph-Negative Chronic Myelogenous Leukemia: A Case for Vigilance in Fluorescence in Situ Hybridization ?nterpretation,” Cancer, Genetics and Cytogenetics, Vol. 104, 1998, pp. 57-60. doi:10.1016/S0165-4608(97)00430-5
[10] E. Abruzzese, M. J. Pettenati, K. Cox, B. Jackle, R. G. Watts, A. J. Carroll, M. C. Steuterman and P. N. Rao, “Identification of BCR/ABL Fusion on Chromosome 9 by Fluorescence in Situ Hybridization in Two Chronic Myeloid Leukemia Cases,” Cancer, Genetics and Cytogenetics, Vol. 105, 1998, pp. 164-167. doi:10.1016/S0165-4608(98)00020-X
[11] K. S. Reddy and B. Grove, “A Philadelphia-Negative Chronic Myeloid Leukemia with a BCR/ABL Fusion Gene on Chromosome 9,” Cancer, Genetics and Cytogenetics, Vol. 107, No. 1, 1998, pp. 48-50. doi:10.1016/S0165-4608(98)00064-8
[12] H. R. Qiu, K. R. Miao, R. Wang, C. Qiao, J. F. Zhang, S. J. Zhang, S. X. Qian, W. Xu and J. Y. Li, “The Appli- cation of Fluorescence in Situ Hybridization in Detecting Chronic Myeloid Leukemia,” Chinese Journal of Medical Genetics, Vol. 26, No. 2, 2009, pp. 207-210.
[13] T. H. Lim, S. L. Tien, P. Lim and A. S. Lim, “The Incidence and Patterns of BCR/ABL Rearrangements in Chronic Myeloid Leukaemia (CML) Using Fluorescence In situ Hybridisation (FISH),” Annals Academy of Medicine Singapore, Vol. 34, No. 9, 2005, pp. 533-538.
[14] G. W. Dewald, C. R. Schad, E. R. Christensen, A. L. Tiede, A. R. Zinsmeister, S. L. Spurbeck, S. N. Thibo- deau and S. M. Jalal, “The Application of Fluorescent in Situ Hybridization to Detect Mbcr/Abl Fusion in Variant Ph Chromosomes in CML and ALL,” Cancer, Genetics and Cytogenetics, Vol. 71, 1993, pp. 7-14.doi:10.1016/0165-4608(93)90196-S
[15] J. L. Diez-Martin, G. W. Dewald and R. V. Pierre, “Possible Cytogenetic Distinction between Lymphoid and Myeloid Blast Crisis in Chronic Granulocytic Leukemia”, American Journal of Hematology, Vol. 27, No. 1, 1988, pp. 194-203. doi:10.1002/ajh.2830270309
[16] P. B. Sinclair, E. P. Nacheva, M. Leversha, N. Telford, J. Chang, A. Reid, A. Bench, K. Champion, B. Huntly and A. R. Gren, “Large Deletions at the T(9; 22) Breakpoint are Common and may ?dentify a Poor-Prognosis Subgroup of Patients with Chronic Myeloid Leukemia,” Blood, Vol. 95, 2000, pp. 738-743.
[17] C. Herens, F. Tassin, V. Lemaire, Y. Beguin, E. Collard, S. Lampertz, C. Croisiau, M. Lecomte, B. De Prijk, L. Longrée and L. Koulischer, “Deletion of the 5’-ABL Region: A Recurrent Anomaly Detected by Fluorescence in Situ Hybridization in About 10% of Philadelphia- Positive Chronic Myeloid Leukaemia Patients,” British Journal of Haematology, Vol. 110, No. 1, 2000, pp. 214-216. doi:10.1046/j.1365-2141.2000.02142.x
[18] B. J. Huntly, A. G. Reid, A. J. Bench, L. J. Campbell, N. Telford, P. Shepherd, J. Szer, H. M. Prince, P. Turner, C. Grace, E. P. Nacheva and A. R. Gren, “Deletions of the Derivative Chromosome 9 Occur at the Time of the Philadelphia Translocation and Provide a Powerful and ?ndependent Prognostic ?ndicator in Chronic Myeloid Leukemia,” Blood, Vol. 98, No. 6, 2001, pp. 1732-1738.doi:10.1182/blood.V98.6.1732
[19] N. Cohen, G. Rozenfeld-Granot, I. Hardan, F. Brok- Simoni, N. Amariglio, G. Rechavi and L. Trakhtenbrot, “Subgroup of Patients with Philadelphia-Positive Chronic Myelogenous Leukemias Characterized by a Deletion of 9q Proximal to ABL Gene: Expression Profiling, Resis- tance to ?nterferon Therapy, and Poor Prognosis,” Cancer, Genetics and Cytogenetics, Vol. 128, No. 2, 2001, pp. 114-119. doi:10.1016/S0165-4608(01)00412-5
[20] A. G. Reid, B. J. Huntly, C. Grace, A. R. Green and E. P. Nacheva, “Survival ?mplications of Molecular Heter- ogeneity in Variant Philadelphia-Positive Chronic Myeloid Leukaemia,” British Journal of Haematology, Vol. 121, No. 3, 2003, pp. 419-427.doi:10.1046/j.1365-2141.2003.04291.x
[21] E. Nacheva, T. Holloway, K. Brown, D. Bloxham and A. R. Gren, “Philadelphianegative Chronic Myeloid Leu- kemia: Detection by FISH Of BCR-ABL Fusion Gene Localized Either to Chromosome 9 or Chromosome 22,” British Journal of Haematology, Vol. 87, No. 2, 1994, pp. 409-412. doi:10.1111/j.1365-2141.1994.tb04933.x
[22] A. N. Mohamed, F. Koppitch, M. Varterasian, C. Karanes, K. L. Yao and F. H. Sarkar, “BCR/ABL Fusion Located on Chromosome 9 in Chronic Myeloid Leukemia with a Masked Ph Chromosome,” Genes Chromosome Cancer, Vol. 13, No. 2, 1995, pp. 133-137.doi:10.1002/gcc.2870130210
[23] D. Primo, M. D. Tabernero, A. Rasillo, J. M. Sayagues, A. B. Espinosa, M. C. Chillon, R. Garcia-Sanz, N. Gutierrez, M. Giralt, A. Hagemeijer, J. F. San Miguel and A. Orfao, “Patterns of BCR/ABL Rearrangements by ?nterphase Fluorescence in Situ Hybridization (FISH) in BCR/ABL+ Leukemias: ?ncidence and Underlying Genetic Abnormalities,” Leukemia, Vol. 17, 2003, pp. 1124-1129. doi:10.1038/sj.leu.2402963
[24] H. Lawce, C. Durum, N. Unsworth, S. Olson and R. E. Magenis, “BCR-ABL FISH: Probes, Patterns and Prognosis,” Association of Genetic Technologists, Vol. 28, 2002, pp. 40-46.
[25] B. J. Huntly, A. J. Bench, E. Delabesse, A. G. Reid, J. Li, M. A. Scott, L. Campbell, J. Byrne, E. Pinto, A. Brizard, D. Niedermeiser, E. P. Nacheva, F. Guilhot, M. Deininger and A. R. Gren, “Derivative Chromosome 9 Deletions in Chronic Myeloid Leukemia: Poor Prognosis is not Associated with Loss of ABL-BCR Expression, Elevated BCR-ABL Levels, or Karyotypic ?nstability,” Blood, Vol. 99, No. 12, 2002, pp. 4547-4553. doi:10.1182/blood.V99.12.4547
[26] B. J. Huntly, F. Guilhot, A. G. Reid, G. Vassiliou, E. Hennig, C. Franke, J. Byrne, A. Brizard, D. Niederwieser, J. Freeman-Edward, G. Cuthbert, N. Bown, R. E. Clark, E. P. Nacheva, A. R. Green and M. W. Deininger, “Imatinib ?mproves but May not Fully Reverse the Poor Prognosis of CML Patients with Derivative Chromosome 9 Deletions,” Blood, Vol. 102, No. 6, 2003, pp. 2205-2215.doi:10.1182/blood-2002-09-2763
[27] M. B.-L. Coniat, K. F. Nguyen, M. T. Daniel, O. A. Bernard and R. Berger, “Chromosome 21 Abnormalities with AML1 Amplification in Acute Lymphoblastic Leukemia,” Genes Chromosome Cancer, Vol. 32, No. 3, 2001, pp. 244–249. doi:10.1002/gcc.1188
[28] F. Morel, A. Herry, M.-J. Le Bris, N. Douet-Guilbert, G. Le Calvez, V. Marion, C. Berthou and M. De Braekeeler, “AML1 Amplification in a Case of Childhood Acute Lymphoblastic Leukemia,” Cancer, Genetics and Cytogenetics, Vol. 137, No. 2, 2002, pp. 142-145.doi:10.1016/S0165-4608(02)00566-6
[29] D. Penther, C. Preudhomme, P. Talmant, C. Roumier, A. Godon, F. Mechinaud, N. Milpied, R. Bataille and H. Avet-Loiseau, “Amplification of AML1 Gene is Present in Childhood Acute Lymphoblastic Leukemia but not in Adult, and is not Associated with AML1 Gene Mutation,” Leukemia, Vol. 16, No. 6, 2002, pp. 1131-1134.doi:10.1038/sj.leu.2402479
[30] C. Preudhomme, D. Warot-Loze, C. Roumier, N. Grardel-Duflos, R. Garand, J. L. Lai, N. Dastugue, E. Macintyre, C. Denis, F. Bauters, J. P. Kerckaert, A. Cosson and P. Fenaux, “High ?ncidence of Biallelic Point Mutations in the Runt Domain of the AML1/PEBP2 Alpha B Gene in Mo Acute Myeloid Leukemia and in Myeloid Malignancies with Acquired Trisomy 21,” Blood, Vol. 96, 2000, pp. 2862-2869.
[31] G. W. Dewald, W. A. Wyatt, A. L. Juneau, R. O. Carlson, A. R. Zinsmeister, S. M. Jalal, J. L. Spurbeck and R. T. Silver, “Highly Sensitive Fluorescence in Situ Hybridi- Zation Method to Detect Double BCR/ABL Fusion and Monitor Response to Therapy in Chronic Myeloid Leukemia,” Blood, Vol. 91, No. 9, 1998, pp. 3357-3365.
[32] D. C. van der Plas, A. B. Hermans, D. Soekarman, E. M. Smit, A. de Klein, N. Smadja, G. Alimena, R. Goudsmit, G. Grosveld and A. Hagemeijer, “Cytogenetic and Mole- cular Analysis in Philadelphia Negative CML,” Blood, Vol. 73, No. 4, 1989, pp. 1038-1044.
[33] F. Mitelman, “Recurrent Chromosome Aberrations in Cancer,” Mutat Research, Vol. 462, 2000, pp. 247-253.doi:10.1016/S1383-5742(00)00006-5
[34] W. Xu, X. Cao, Q. Liu, L. Fan, K. R. Mio, H. R. Qiu, D. X. Zhu, H. X. Qiu and J. Y. Li, “Trisomy 8 in Two Newly Diagnosed Chinese Patients with Chronic Lym- phocytic Leukemia,” Cancer, Genetics and Cytogenetics, Vol. 192, No. 2, 2009, pp. 79-81.doi:10.1016/j.cancergencyto.2009.04.007
[35] B. Johansson, T. Fioretos and F. Mitelman, “Cytogenetic and Molecular Genetic Evolution of Chronic Myeloid Leukemia,” Acta Haematologica, Vol. 107, No. 2, 2002, pp. 76-94. doi:10.1159/000046636
[36] J. Anastasi, J. Feng, M. M. Le Beau, L. A. Larson, J. Rowley and J. W. Vardiman, “Cytogenetic Clonality in Myelodysplastic Syndromes Studied with Fluorescemnce in Situ Hybridization: Lineage, Response to Growth Factor Therapy, and Clone Expansion,” Blood, Vol. 81, No. 6, 1993, pp. 1580-1585.

comments powered by Disqus

Copyright © 2018 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.