Cytogenetics abnormalities in acute leukemias of ambiguous lineage: First report of complex variant philadelphia translocations
Abstract
Background: Acute leukemias of ambiguous lineage (ALAL) are incompletely characterized and are very rare, accounts< 4% of acute leukemias . In most leukaemias the cytogenetic and molecular genetic changes have emerged to be diagnostic as well as prognostic importance. Due to Lack of diagnostic criterias, it is difficult to establish cytogenetic features in ALAL. In present study we reviewed chromosomal aberrations, their molecular background, their prognostic relevance of ALAL & summarized some new chromosome aberrations along with probable mechanism of complex variant translocation.
Design and Methods: Present study from Kidwai state cancer institute concentrated on cytogenetic findings of ALAL, especially B+Myeloid MPAL cases, more so regarding complex variant phildelphia chromosome translocations summarised diagnostic criteria based on WHO 2008 classification, clinical, immunophenotyping and molecular features, along with treatment & follow up.
Results: Among 32 cases of ALAL cases, 28 MPAL cases reported in the present study 13 cases were B/Myeloid, followed by B+T MPAL, T+Myeloid .4 cases of undifferentiated and unclassifiable leukemias were reported. B/myeloid MPAL were in majority, 13 cases. Cytogenetics abnormality was detected in 4 cases of B/myeloid MPAL. 3 cases were Ph +, another case was hyperdiploid, surprisingly out of 3 Ph+ cases, 2 cases (66.6%) showed complex variant Phildelphia chromosome.
Conclusion: B+MYELOID MPAL revealed significant cytogenetic abnormalities. Although Ph+ is reported in MPAL, complex variant Ph with 4 or 3 way translocations are not reported in ALAL especially in B/Myeloid MPAL .Immunophenotyping & cytogenetics in ALAL should be mandatory. Multiple levels of genetic heterogeneity exist in these leukemias with variant Ph translocations. Prognosis improves when treated with Imatinib.
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References
2. Borowitz M J Bene MC,HarrisNL,PorwitA,Matutes E Acute leukemia of ambiguous lineage :WHO classification of hematopoietic and lymphoid tissue 4th ed.IARC,Lyon,France:2008.p 150-55.
3. Huret JL. Complex translocations, simple variant translocations and Ph-negative cases in chronic myelogenous leukaemia. Hum Genet. 1990 Oct;85(6):565-8.
4. Milelman, F The cytogenetic scenario of chronic myeloid leukemia. Leukemia and Lymphoma.1993; 11:11-15.
5. Al-Seraihy, A.S., Owaidah, T.M., Ayas, M., El-Solh, H., Al-Mahr, M., Al-Ahmari, A. &Belgaumi, A.F.Clinical characteristics and outcome of children with biphenotypic acute leukaemia.Haematologica, 2009 ;94:1682-90.
6. Matutes, E., Pickl, W.F., Van’t Veer M., Morilla, R., Swansbury, J., Strobl, H., Attarbaschi, A., Hopfinger, (i., Ashley, S., Bene, M.C., Porwit, A., Orfao, A., Lemez, P., Schabath, R. & Ludwig, W.D. Mixed-phenotype acute leukaemia: clinical and laboratory features and outcome in 100 patients defined according to the WHO 2008 classification, Blood.2011;117: 3163-71.
7. Prateek Bhatia, JogeshwarBinota, Neelam Varma, Deepak Bansal, AmitaTrehan, Ram Kumar Marwaha, Pankaj Malhotra and Subhash Varma.A Study on the Expression of BCR-ABL Transcript in Mixed Phenotype Acute Leukemia (MPAL) Cases Using the Reverse Transcriptase Polymerase Reaction Assay (RT-PCR) and its Correlation with Hematological Remission Status Post Initial Induction Therapy. Mediterr J Hematol Infect Dis 2012;4(1): e2012024, DOI 10.4084/MJHID. 2012,024.
8. Gerr, H., Zimmermann, M., Schrappe, M., Dworzak, M., Ludwig, W.D., Bradtke, J., Moericke. A., Schabath, R., Creutzig, U. & Reinhardt, D.Acute leukaemias of ambiguous lineage in children: characterization, prognosis and therapy recommdendations. British Journal of Haematology,2010; 149: 84-92.
9. Park, T.S., Lee, S.T., Song, J., Lee, K.A., Kim, J., Park, Y., Song,S. & Choi, J.R. Biphenotypic acute leukaemia with b2a2 fusion transcript and trisomy 21.Cancer Genetics and Cytogenetics.2009b; 188:129-131.
10. Cuneo, A., Ferrant, A., Michaux, J.L., Bosly, A., Chatelain, B., Stul, M., Dal Cin, P., Dierlamm, J., Cassiman, J.J., Hossfeld, D.K., Castoldi, G. & Van den Berghe, H. Cytogenetic and clinicobiological features of acute leukaemia with stem cell phenotype: study of nine cases. Cancer Genetics and Cytogenetics,1996; 92: 31-36.
11. Heesch,SNeumannschwartz,s,bartram,Schlee.c,Burmeister,T,Hanel etal Acute leukemias of Ambiguous lineage in adults:moiecular and clinical characterization.Annals of Hematology.2013;92:747-58.
12. Wang, Y., Gu, M., Y., Qiu, L., Bian, S. & Wang. J. Clinical characteristics and outcomes of mixed phenotype acute leukaemia with Philadelphia chromosome positive and/or bcr-abl positive in adult. International Journal of Hematology.2011; 94: 552-55.
13. Hagemeijer, A., Bartram, C.R., E.M., van Agthoven, A.J. &Bootsma. D. Is the chromosomal region 9q34 always involved in variants of the Ph1 translocation? Cancer Genetics and Cytogenetics.1984;13:1-16.
14. Morris, C.M., Rosman, I., Archer, S.A., Cohranse, J.M. & Fitzgerald, P.H .A cytogenetic and molecular analysis of five variant Philadelphia translocations in chronic myeloid leukemia. Cancer Genetics and Cytogenetics 1988;35: 179-197.
15. Sessarego, M., Fugazza, G., Bruzzone, R., Ballestrero, A., Miglino, M. &Bacigalupo, A. Complex chromosome rearrangements may locate the bcr/abl fusion gene sites other than 22q11. Haematologica, 2000;85:35-39.
16. Heim, S., Billstrom, R., Kristoffersson, U., Mandahl, N., Strombeck, B. &Mitelman, F.Variant Ph translocations in chronic myeloid leukemia.Cancer Genetics and Cytogenetics. 1985;18:215-227.
17. Huret, J.L. &Tanzer.J. Non-random aberrant breakpoints in chronic myelogenous leukaemia revisited. A call for a collaborative study. Human Genetics.1989; 83: 208.
18. Fitzgerald, P.H. & Morris, C.M. Complex chromosomal translocations in the Philadelphia chromosome leukemias.Serial translocations or a concerted genomic rearrangement?Cancer genetics and Cytogenetics.1991; 57: 143-151.
19. Calbrese, G., Stuppia, L., Franchi, P.G.,Peila, R., Morisio, E., Liberati, A.M., Spadano, A., Di Lorenso, R., Donti, E. &Antonucci, A. Complex translocations of the Ph chromosome and Ph negative CML arise from similar mechanisms, as evidenced by FISH analysis. Cancer Genetics and Cytogenetics(1994); 78:153-9.
20. AlistaigG.Reid, Brian J.P. Huntly, Colin Grace, Anthony R. Green and Elisabeth P. Nacheva. Survival implications of molecular heterogeneity in variant Philadelphia-positive chronic myeloid leukaemia.
British Journal of Haematology 2003, 121, 419-27.
21. Yehuda, O., Abeliovich, D., Ben-Neriah,S., Sverdlin, I., Cohen, R., Varadi, G., Orr, R., Ashkenazi, Y.J., Heyd, J., Lugassy, G. & Ben Yehuda, D. Clinical implications of fluorescence in situ hybridizations analysis in 13 chronic myeloid leukemia cases: Ph-negative and variant Ph-positive. Cancer Genetics and Cytogenetics.1999; 114: 100-7.
22. M .M. T.el-Zimaity,H,Kantarjian,M.Talpaz et al.,’Results of imatinib mesylate therapy in chronic myelogenous leukemia with variant Phildelphia chromosome’’British Journal of Haematology. 2004;vol 25: no2, 187-195.
23. G.Marzocchi,E Castagnetti and SLuatti. Vriant phildelphia translocations:molecular-cytogenetic characterisation and prognostic influence on frontline imatinib therapy,a GIMEMA Working Party on CML analysis’’.Blood;2011:vol117,no25,6793-800.
24. Masahiro Manabe, Yumi Yoshii, Satoru Mukai, Erina Sakamoto, Hiroshi Kanashima, Takeshi Inoue, and Hirofumi Teshima. A Rare t(9;22;16) (q34;q11;q24) Translocation in Chronic Myeloid Leukemia for Which Imatinib Mesylate Was Effective: A Case Report. Leukemia Research and Treatment Volume 2011; Article ID 592519, 3 pages doi: 10.4061/2011/592519.
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