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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2015

Open Access 01-12-2015 | Research

Chromosomal rearrangement involving 11q23 locus in chronic myelogenous leukemia: a rare phenomenon frequently associated with disease progression and poor prognosis

Authors: Wei Wang, Guilin Tang, Jorge E Cortes, Hui Liu, Di Ai, C Cameron Yin, Shaoying Li, Joseph D Khoury, Carlos Bueso-Ramos, L Jeffrey Medeiros, Shimin Hu

Published in: Journal of Hematology & Oncology | Issue 1/2015

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Abstract

Background

Progression of chronic myelogenous leukemia (CML) is frequently accompanied by cytogenetic evolution, commonly unbalanced chromosomal changes, such as an extra copy of Philadelphia chromosome (Ph), +8, and i(17)(q10). Balanced chromosomal translocations typically found in de novo acute myeloid leukemia occur occasionally in CML, such as inv(3)/t(3;3), t(8;21), t(15;17), and inv(16). Translocations involving the 11q23, a relatively common genetic abnormality in acute leukemia, have been seldom reported in CML. In this study, we explored the prevalence and prognostic role of 11q23 in CML.

Methods

We searched our pathology archives for CML cases diagnosed in our institution from 1998 to present. Cases with 11q23 rearrangements were retrieved. The corresponding clinicopathological data were reviewed.

Results

A total of 2,012 cases of CML with available karyotypes were identified. Ten (0.5%) CML cases had 11q23 rearrangement in Ph-positive cells, including 4 cases of t(9;11), 2 cases of t(11;19), and 1 case each of t(2;11), t(4;11), t(6;11), and t(4;9;11). Eight cases (80%) had other concurrent chromosomal abnormalities. There were 6 men and 4 women with a median age of 50 years (range, 21–70 years) at time of initial diagnosis of CML. 11q23 rearrangement occurred after a median period of 12.5 months (range, 0–172 months): 1 patient in chronic phase, 2 in accelerated phase, and 7 in blast phase. Eight of ten patients died after a median follow-up of 16.5 months (range, 8–186 months) following the initial diagnosis of CML, and a median of 6.7 months (range, 0.8–16.6 months) after the emergence of 11q23 rearrangement. The remaining two patients had complete remission at the last follow-up, 50.2 and 6.9 months, respectively. In addition, we also identified a case with 11q23/t(11;17) in Ph-negative cells in a patient with a history of CML. MLL involvement was tested by fluorescence in situ hybridization in 10 cases, and 7 cases (70%) were positive.

Conclusions

In summary, chromosomal rearrangements involving 11q23 are rare in CML, frequently occurring in blast phase, and are often associated with other cytogenetic abnormalities. These patients had a low response rate to tyrosine kinase inhibitors and a poor prognosis.
Literature
1.
Hehlmann R. How I, treat CML blast crisis. Blood. 2012;120(4):737–47. doi:10.1182/blood-2012-03-380147.CrossRefPubMed
2.
Quintas-Cardama A, Cortes J. Molecular biology of bcr-abl1-positive chronic myeloid leukemia. Blood. 2009;113(8):1619–30. doi:10.1182/blood-2008-03-144790.CrossRefPubMedCentralPubMed
3.
Mu Q, Ma Q, Wang Y, Chen Z, Tong X, Chen FF, et al. Cytogenetic profile of 1,863 Ph/BCR-ABL-positive chronic myelogenous leukemia patients from the Chinese population. Ann Hematol. 2012;91(7):1065–72. doi:10.1007/s00277-012-1421-6.CrossRefPubMed
4.
Haferlach C, Bacher U, Schnittger S, Weiss T, Kern W, Haferlach T. Similar patterns of chromosome abnormalities in CML occur in addition to the Philadelphia chromosome with or without tyrosine kinase inhibitor treatment. Leukemia. 2010;24(3):638–40. doi:10.1038/leu.2009.222.CrossRefPubMed
5.
Aydin C, Cetin Z, Salim O, Yucel OK, Undar L, Berker KS. Previously unreported chromosomal aberrations of t(3;3)(q29;q23), t(4;11)(q21;q23), and t(11;18)(q10;q10) in a patient with accelerated phase Ph + CML. Case reports in genetics. 2014;2014:582016. doi:10.1155/2014/582016.CrossRefPubMedCentralPubMed
6.
Dastugue N, Duchayne E, Huguet F, Demur C, Plaisancie H, Calvas P, et al. t(9;11)(p22;q23) translocation in blastic phase of chronic myeloid leukemia. Cancer Genet Cytogenet. 1992;63(1):37–42.CrossRefPubMed
7.
Haus O, Noworolska A, Laskowski M, Kuliszkiewicz-Janus M, Kozlowska J, Harlozinska-Szmyrka A, et al. Prognostic significance of secondary cytogenetic changes and nonspecific cross-reacting antigen (NCA) in patients with Ph-positive chronic myeloid leukemia. Exp Mol Pathol. 1990;52(2):235–42.CrossRefPubMed
8.
Li L, Ritterbach J, Harbott J, Schroyens W, Lohmeyer J, Pralle H, et al. Blastic phase chronic myeloid leukemia with a four-break rearrangement: t(11;9)(9;22)(q23;p22q34;q11). Cancer Genet Cytogenet. 1993;68(2):131–4.CrossRefPubMed
9.
Nishii K, Usui E, Sakakura M, Miyata E, Ridge SA, Ford AM, et al. Additional t(11;17)(q23;q21) in a patient with Philadelphia-positive mixed lineage antigen-expressing leukemia. Cancer Genet Cytogenet. 2001;126(1):8–12.CrossRefPubMed
10.
Otero L, Moellmann AC, Pombo-de-Oliveira MS, Ornellas MH, Pires V, Bouzas LF, et al. Additional t(1;11)(q21;q23) with mixed lineage leukemia rearrangement in T-blastic crisis of a Ph-positive chronic myeloid leukemia. Eur J Haematol. 2007;79(2):179–81. doi:10.1111/j.1600-0609.2007.00884.x.CrossRefPubMed
11.
Rajcan-Separovic E, Bence-Bruckler I, Wells P, Wang H. Fluorescence in situ hybridization analysis of complex translocations in two newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia patients. Cancer Genet Cytogenet. 1999;114(1):71–4.CrossRefPubMed
12.
Royer-Pokora B, Hildebrandt B, Redmann A, Herold C, Kronenwett R, Haas R, et al. Simultaneous occurrence of a t(9;22) (Ph) with a t(2;11) in a patient with CML and emergence of a new clone with the t(2;11) alone after imatinib mesylate treatment. Leukemia. 2003;17(4):807–10. doi:10.1038/sj.leu.2402877.CrossRefPubMed
13.
Suzuki K, Sugawara T, Kowata S, Utsugizawa T, Ito S, Murai K, et al. Uncommon karyotypic abnormality, t(11;19)(q23;p13.3), in a patient with blastic phase of chronic myeloid leukemia. Cancer Genet Cytogenet. 2004;150(2):159–63. doi:10.1016/j.cancergencyto.2003.09.005.CrossRefPubMed
14.
Zamecnikova A. Acquisition of mixed lineage leukemia rearrangement in a chronic myeloid leukemia patient while on imatinib. Hematology reports. 2011;3(2):e13.CrossRefPubMedCentralPubMed
15.
Armstrong SA, Look AT. Molecular genetics of acute lymphoblastic leukemia. J Clin Oncol. 2005;23(26):6306–15. doi:10.1200/JCO.2005.05.047.CrossRefPubMed
16.
Tomizawa D, Koh K, Sato T, Kinukawa N, Morimoto A, Isoyama K, et al. Outcome of risk-based therapy for infant acute lymphoblastic leukemia with or without an MLL gene rearrangement, with emphasis on late effects: a final report of two consecutive studies, MLL96 and MLL98, of the Japan Infant Leukemia Study Group. Leukemia. 2007;21(11):2258–63. doi:10.1038/sj.leu.2404903.CrossRefPubMed
17.
Schoch C, Schnittger S, Klaus M, Kern W, Hiddemann W, Haferlach T. AML with 11q23/MLL abnormalities as defined by the WHO classification: incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases. Blood. 2003;102(7):2395–402. doi:10.1182/blood-2003-02-0434.CrossRefPubMed
18.
Meyer C, Hofmann J, Burmeister T, Groger D, Park TS, Emerenciano M, et al. The MLL recombinome of acute leukemias in 2013. Leukemia. 2013;27(11):2165–76. doi:10.1038/leu.2013.135.CrossRefPubMedCentralPubMed
19.
Zeisig BB, Schreiner S, Garcia-Cuellar MP, Slany RK. Transcriptional activation is a key function encoded by MLL fusion partners. Leukemia. 2003;17(2):359–65. doi:10.1038/sj.leu.2402804.CrossRefPubMed
20.
21.
Harper DP, Aplan PD. Chromosomal rearrangements leading to MLL gene fusions: clinical and biological aspects. Cancer Res. 2008;68(24):10024–7. doi:10.1158/0008-5472.CAN-08-2208.CrossRefPubMedCentralPubMed
22.
Manara E, Baron E, Tregnago C, Aveic S, Bisio V, Bresolin S, et al. MLL-AF6 fusion oncogene sequesters AF6 into the nucleus to trigger RAS activation in myeloid leukemia. Blood. 2014;124(2):263–72. doi:10.1182/blood-2013-09-525741.CrossRefPubMed
23.
Cortes J, Talpaz M, O’Brien S, Rios MB, Majlis A, Keating M, et al. Suppression of cytogenetic clonal evolution with interferon alfa therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. J Clin Oncol. 1998;16(10):3279–85.PubMed
24.
Cortes JE, Talpaz M, Giles F, O’Brien S, Rios MB, Shan J, et al. Prognostic significance of cytogenetic clonal evolution in patients with chronic myelogenous leukemia on imatinib mesylate therapy. Blood. 2003;101(10):3794–800. doi:10.1182/blood-2002-09-2790.CrossRefPubMed
25.
O’Dwyer ME, Mauro MJ, Kurilik G, Mori M, Balleisen S, Olson S, et al. The impact of clonal evolution on response to imatinib mesylate (STI571) in accelerated phase CML. Blood. 2002;100(5):1628–33. doi:10.1182/blood-2002-03-0777.CrossRefPubMed
26.
Verma D, Kantarjian H, Shan J, O’Brien S, Estrov Z, Garcia-Manero G, et al. Survival outcomes for clonal evolution in chronic myeloid leukemia patients on second generation tyrosine kinase inhibitor therapy. Cancer. 2010;116(11):2673–81. doi:10.1002/cncr.25015.PubMedCentralPubMed
27.
Fabarius A, Leitner A, Hochhaus A, Muller MC, Hanfstein B, Haferlach C, et al. Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV. Blood. 2011;118(26):6760–8. doi:10.1182/blood-2011-08-373902.CrossRefPubMed
28.
Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122(6):872–84. doi:10.1182/blood-2013-05-501569.CrossRefPubMed
29.
Giugliano E, Rege-Cambrin G, Scaravaglio P, Wlodarska I, Emanuel B, Stul M, et al. Two new translocations involving the 11q23 region map outside the MLL locus in myeloid leukemias. Haematologica. 2002;87(10):1014–20.PubMed
30.
Cox MC, Panetta P, Lo-Coco F, Del Poeta G, Venditti A, Maurillo L, et al. Chromosomal aberration of the 11q23 locus in acute leukemia and frequency of MLL gene translocation: results in 378 adult patients. Am J Clin Pathol. 2004;122(2):298–306. doi:10.1309/RX27-R8GJ-QM33-0C22.CrossRefPubMed
31.
Kornblau SM, Qiu YH, Zhang N, Singh N, Faderl S, Ferrajoli A, et al. Abnormal expression of FLI1 protein is an adverse prognostic factor in acute myeloid leukemia. Blood. 2011;118(20):5604–12. doi:10.1182/blood-2011-04-348052.CrossRefPubMedCentralPubMed
32.
Baud V, Lipinski M, Rassart E, Poliquin L, Bergeron D. The human homolog of the mouse common viral integration region, FLI1, maps to 11q23-q24. Genomics. 1991;11(1):223–4.CrossRefPubMed
33.
Loriaux M, Deininger M. Clonal cytogenetic abnormalities in Philadelphia chromosome negative cells in chronic myeloid leukemia patients treated with imatinib. Leuk Lymphoma. 2004;45(11):2197–203. doi:10.1080/10428190410001723278.CrossRefPubMed
34.
Jabbour E, Kantarjian HM, Abruzzo LV, O’Brien S, Garcia-Manero G, Verstovsek S, et al. Chromosomal abnormalities in Philadelphia chromosome negative metaphases appearing during imatinib mesylate therapy in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Blood. 2007;110(8):2991–5. doi:10.1182/blood-2007-01-070045.CrossRefPubMed
35.
Kovitz C, Kantarjian H, Garcia-Manero G, Abruzzo LV, Cortes J. Myelodysplastic syndromes and acute leukemia developing after imatinib mesylate therapy for chronic myeloid leukemia. Blood. 2006;108(8):2811–3. doi:10.1182/blood-2006-04-017400.CrossRefPubMed
36.
Perel JM, McCarthy C, Walker O, Irving I, Williams B, Kennedy GA. Clinical significance of development of Philadelphia-chromosome negative clones in patients with chronic myeloid leukemia treated with imatinib mesylate. Haematologica. 2005;90 Suppl:ECR25.
37.
Bacher U, Hochhaus A, Berger U, Hiddemann W, Hehlmann R, Haferlach T, et al. Clonal aberrations in Philadelphia chromosome negative hematopoiesis in patients with chronic myeloid leukemia treated with imatinib or interferon alpha. Leukemia. 2005;19(3):460–3. doi:10.1038/sj.leu.2403607.CrossRefPubMed
38.
Andersen MK, Pedersen-Bjergaard J, Kjeldsen L, Dufva IH, Brondum-Nielsen K. Clonal Ph-negative hematopoiesis in CML after therapy with imatinib mesylate is frequently characterized by trisomy 8. Leukemia. 2002;16(7):1390–3. doi:10.1038/sj.leu.2402634.CrossRefPubMed
39.
Chee YL, Vickers MA, Stevenson D, Holyoake TL, Culligan DJ. Fatal myelodysplastic syndrome developing during therapy with imatinib mesylate and characterised by the emergence of complex Philadelphia negative clones. Leukemia. 2003;17(3):634–5. doi:10.1038/sj.leu.2402842.CrossRefPubMed
40.
Quintas-Cardama A, Kantarjian H, Abruzzo LV, Cortes J. Extramedullary BCR-ABL1-negative myeloid leukemia in a patient with chronic myeloid leukemia and synchronous cytogenetic abnormalities in Philadelphia-positive and -negative clones during imatinib therapy. Leukemia. 2007;21(11):2394–6. doi:10.1038/sj.leu.2404865.CrossRefPubMed
41.
Perrotti D, Jamieson C, Goldman J, Skorski T. Chronic myeloid leukemia: mechanisms of blastic transformation. J Clin Invest. 2010;120(7):2254–64. doi:10.1172/JCI41246.CrossRefPubMedCentralPubMed
42.
Lee SG, Park TS, Oh SH, Park JC, Yang YJ, Marschalek R, et al. De novo acute myeloid leukemia associated with t(11;17)(q23;q25) and MLL-SEPT9 rearrangement in an elderly patient: a case study and review of the literature. Acta Haematol. 2011;126(4):195–8. doi:10.1159/000329389.CrossRefPubMed
Metadata
Title
Chromosomal rearrangement involving 11q23 locus in chronic myelogenous leukemia: a rare phenomenon frequently associated with disease progression and poor prognosis
Authors
Wei Wang
Guilin Tang
Jorge E Cortes
Hui Liu
Di Ai
C Cameron Yin
Shaoying Li
Joseph D Khoury
Carlos Bueso-Ramos
L Jeffrey Medeiros
Shimin Hu
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2015
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-015-0128-2

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