Cytogenetic Abnormalities with Interphase FISH Method and Clinical Manifestation in Chronic Lymphocytic Leukemia Patients in North-East of Iran
-
Hossein Rahimi
,
Mohammad Hadi Sadeghian
,
Mohammad Reza Keramati
,
Amir Hossein Jafarian
,
Sepideh Shakeri
,
Seyyede Fatemeh Shams
,
Neda Motamedi
,
Maryam Sheikhi
,
Hossein Ayatollahi
Abstract
Background: Chronic lymphocytic leukemia (CLL) is one of the most prevalent adult leukemias. This malignancy is known by lymphocytosis for a duration of more than 3 months. In fact, it is a heterogeneous clinical disease with changeable progression. Chromosomal aberrations are significant parameters to predict result and survival rate and find treatment strategies for each patient. Cytogenetic methods are known as sensitive and relatively new procedures to detect abnormalities in genome.
Subjects and Methods: In order to identify CLL-related chromosomal abnormalities, 48 CLL patients included 38 Men and 10 Women with mean age of 58.25±36 were enrolled in this case series study. The survey was done at Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences. Interphase fluorescent in situ hybridization (I-FISH) was done on unstimulated peripheral blood or bone marrow samples, which were cultured in whole medium culture; it was used to detect chromosomal abnormalities such as 11q- , 13q14-, 17p- , 6q- and trisomy 12 in CLL patients.
Results: Analysis demonstrated that 45.5% of CLL cases had chromosomal abnormalities; 13.63% had del 17p, 40.90% had del 13q14 and 9.09% had del 11q. Statistical analysis of data revealed a significant relevancy between age variable and splenomegaly occurrence (P value<0.05). The younger the patients were, the less the splenomegaly occurrence.
Conclusion: Laboratory findings were correlated with clinical data.
Coll-Mulet L, Gil J. Genetic alterations in chronic lymphocytic leukaemia. ClinTranslOncol. 2009;11(4):194-8.
Šindelářová L, Michalová K, Zemanová Z, .et al. Incidence of chromosomal anomaliesdetected with FISH and their clinical correlations in B-chronic lymphocytic leukemia. Cancer genet and cytogenet.2005;160(1):27-34.
Wren C, Moriarty H, Marsden K, et al. Cytogenetic investigations of chronic
lymphocytic leukemia. Cancer genet and cytogenet. 2010;198(2):155-61.
Teimori H, Ashoori S, Akbari MT, .et al. FISH Analysis for del6q21 and del17p13 in B-
cell Chronic Lymphocytic Leukemia in Iranians. Iran Red Crescent Med J.
;15(2):107-12.
Puiggros A, Blanco G, Espinet B. Genetic Abnormalities in Chronic LymphocyticLeukemia: where we are and where we go. Biomed Res Int. 2014; 435983.
Dِhner H, Stilgenbauer S, Benner A, .et al. Genomic aberrations and survival in chronic
lymphocytic leukemia. N Engl J Med. 2000;343(26):1910-6.
Binet J, Leporrier M, Dighiero G, et al. A clinical staging system for chronic lymphocytic
leukemia. Prognostic significance. Cancer. 1977;40(2):855-64.
Rai KR, Sawitsky A, Cronkite EP, .et al. Clinical staging of chronic lymphocytic
leukemia. Blood. 1975;46(2):219-34.
Dicker F, Schnittger S, Haferlach T, .et al. Immunostimulatory oligonucleotide-induced
metaphasecytogenetics detect chromosomal aberrations in 80% of CLL patients: a study of 132 CLL cases with correlation to FISH, IgVH status, and CD38 expression. Blood. 2006;108(9):3152-60
Moreno C, Montserrat E. New prognostic markers in chronic lymphocytic leukemia.Blood Rev. 2008;22(4):211-9.
Rai KR, Dِhner H, Keating MJ, .et al. Chronic lymphocytic leukemia: case-based session.ASH Education Program Book. 2001;2001:140-56.
Stevens-Kroef MJ, van den Berg E, OldeWeghuis D . Identification of prognostic relevant chromosomal abnormalities in chronic lymphocytic leukemia using microarray-based genomic profiling.molcytogenet. 2014;7(1):3-21.
Rigolin GM, Cibien F, Martinelli S, .et al. Chromosome aberrations detected by conventional karyotyping using novel mitogens in chronic lymphocytic leukemia with “normal” FISH:correlations with clinicobiologic parameters. Blood. 2012;119(10):2310-3.
Stilgenbauer S, Bullinger L, Benner A, .et al. Incidence and clinical significance of 6qdeletions in B cell chronic lymphocytic leukemia. Leukemia. 1999;13(9):1331-4.
Berkova A, Zemanova Z, Trneny M, .et al. Clonal evolution in chronic lymphocytic leukemia studied by interphase fluorescence in-situ hybridization. Neoplasma. 2009;56(5):455-8.
Reddy K. Chronic lymphocytic leukaemia profiled for prognosis using a fluorescence in situ hybridisation panel. Br J Haematol. 2006;132(6):705-22.
Turgut B, Vural O, Pala FS, .et al. 17p Deletion is associated with resistance of B-cell chronic lymphocytic leukemia cells to in vitro fludarabine-induced apoptosis. Leuk Lymphoma 2007;48(2):311-20.
Baliakas P, Iskas M, Gardiner A, .et al. Chromosomal translocations and karyotypecomplexity in chronic lymphocytic leukemia: a systematic reappraisal of classic cytogenetic data. Am J Hematol. 2014;89(3):249-55.
Stilgenbauer S BL, Lichter P, Dohner H; the German CLL Study Group (GCLLSG).Genetics of chronic lymphocytic leukemia:genomic aberrations and VH gene mutation status in pathogenesis and clinical course. leukemia. 2002;16(6):993-1007.
Smoley SA, Van Dyke DL, Kay NE, .et al. Standardization of fluorescence in situ hybridization studies on chronic lymphocytic leukemia (CLL) blood and marrow cells by the CLL Research Consortium. Cancer Genet Cytogenet. 2010;203(2):141-8.
Calin GA, Dumitru CD, Shimizu M, .et al. Frequent deletions and down-regulation ofmicro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. ProcNatlAcadSci U S A. 2002;99(24):15524-9.
Klein U, Lia M, Crespo M, .et al. The DLEU2/miR-15a/16-1 cluster controls B cellproliferation and its deletion leads to chronic lymphocytic leukemia. Cancer cell. 2010;17(1):28-40.
Mosca L, Fabris S, Lionetti M, .et al. Integrative genomics analyses reveal molecularlydistinct subgroups of B-cell chronic lymphocytic leukemia patients with 13q14 deletion. Clin Cancer Res. 2010;16(23):5641-53.
Rodrguez AE, Hernndez J, Benito R, .et al. Molecular characterization of chroniclymphocytic leukemia patients with a high number of losses in 13q14. PLoS One. 2012;7(11):e48485.
Marasca R, Maffei R, Martinelli S, .et al. Clinical heterogeneity of de novo 11q deletionchronic lymphocytic leukaemia: prognostic relevance of extent of 11q deleted nuclei inside leukemic clone. HematolOncol. 2013;31(2):88-95.
Zenz T, Mertens D, Kuppers R, .et al From pathogenesis to treatment of chronic lymphocytic leukaemia. Nat.Rev.Cancer. 2010:9(12):10:37-50.
Ouillette P, Li J, Shaknovich R, .et al. Incidence and clinical implications of ATM aberrations in chronic lymphocytic leukemia. Genes, Chromosomes and Cancer. 2012;51(12):1125-32.
Rossi D, Fangazio M, Rasi S, .et al. Disruption of BIRC3 associates with fludarabinechemorefractoriness in TP53 wild-type chronic lymphocytic leukemia. Blood. 2012;119(12):2854-62.
Rose-Zerilli MJ, Forster J, Parker H,.et al. ATM mutation rather than BIRC3 deletion and/or mutation predicts reduced survival in 11q-deleted chronic lymphocytic leukemia: data from the UK LRF CLL4 trial. Haematologica. 2014 Apr;99(4):736-42.
Tsimberidou AM, Tam C, Abruzzo LV, .et al. Chemoimmunotherapy may overcome the adverse prognostic significance of 11q deletion in previously untreated patients with chronic lymphocytic leukemia. Cancer. 2009;115(2):373-80.
Delgado J, Espinet B, Oliveira AC, .et al. Chronic lymphocytic leukaemia with 17p deletion: a retrospective analysis of prognostic factors and therapy results. Br J Haematol. 2012;157(1):67-74.
Stilgenbauer S, Zenz T, Winkler D,.etal. Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses fromthe CLL2H study of the German Chronic Lymphocytic Leukemia Study Group. J ClinOncol.. 2009;27(24):3994-4001
Wawrzyniak E, Kotkowska A, Blonski JZ, .et al. Clonal evolution in CLL patients as
detected by FISH versus chromosome banding analysis, and its clinical significance. Eur J Haematol.. 2014;92(2):91-101.
Landau DA, Carter SL, Stojanov P, .et al. Evolution and impact of subclonal mutations
in chronic lymphocytic leukemia. Cell. 2013;152(4):714-26.
Tam CS, Shanafelt TD, Wierda WG, .et al. De novo deletion 17p13. 1 chronic
lymphocytic leukemia shows significant clinical heterogeneity: the MD Anderson and Mayo
Clinic experience. Blood. 2009;114(5):957-64.
Quijano S, Lopez A, Rasillo A, et al. Impact of trisomy 12, del (13q), del (17p), and del
(11q) on the immunophenotype, DNA ploidy status, and proliferative rate of leukemic B‐cells in
chronic lymphocytic leukemia. Cytometry Part B: Cytometry B ClinCytom.. 2008;74(3):139-49.
A. Kr¨ober JB, S. HafnerHafner S, Bühler A, .et al. Additional genetic high-risk features
such as 11q deletion, 17p deletion, and V3- 21 usage characterize discordance of ZAP-70 and
VH mutation status in chronic lymphocytic leukemia. J Clin Oncol.2006;24(6):1923-30.
Rassenti LZ, Jain S, Keating MJ, .et al. Relative value of ZAP-70, CD38, and
immunoglobulin mutation status in predicting aggressive disease in chronic lymphocytic
leukemia. Blood. 2008;112(5):1923-30.
Baliakas P1, Iskas M, Gardiner A,.et al. Chromosomal translocations and karyotype complexity in chronic lymphocytic leukemia: a systematic reappraisal of classic cytogenetic data.Am J Hematol. 2014;89(3):249-55.
Jain N, O'Brien S. Chronic lymphocytic leukemia with deletion 17p: emerging treatment options. Oncology (Williston Park). 2012;26(11):1067, 70.
Gonzalez D, Martinez P, Wade R, .et al. Mutational status of the TP53 gene as a predictor
of response and survival in patients with chronic lymphocytic leukemia: results from the LRF
CLL4 trial. J ClinOncol. 2011;29(6):2223-9.
Gribben JG. Molecular profiling in CLL. ASH Education Program Book. 2008;2008:444
| Files | ||
| Issue | Vol 11, No 3 (2017) | |
| Section | Original Article(s) | |
| Keywords | ||
| Chromosomal aberration chronic lymphocytic leukemia (CLL) Interphase FISH (I-FISH) Polymerase chain reaction (PCR) | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
