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

Journal of Hematology & Oncology, Apr 2015

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.

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

Wang et al. Journal of Hematology & Oncology Chromosomal rearrangement involving 11q23 locus in chronic myelogenous leukemia: a rare phenomenon frequently associated with disease progression and poor prognosis Wei Wang 0 Guilin Tang 0 Jorge E Cortes 1 Hui Liu 0 Di Ai 0 C Cameron Yin 0 Shaoying Li 0 Joseph D Khoury 0 Carlos Bueso-Ramos 0 L Jeffrey Medeiros 0 Shimin Hu 0 0 Department of Hematopathology, The University of Texas MD Anderson Cancer Center , Houston, TX 77030 , USA 1 Department of Leukemia, The University of Texas MD Anderson Cancer Center , Houston, TX 77030 , USA 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. Chronic myelogenous leukemia; BCR-ABL1; Blast phase; Clonal evolution; 11q23; MLL - Background BCR-ABL1 derived from t(9;22)(q34;q11), its variant translocations, or cryptic fusions is the sole chromosomal abnormality in about 8090% of chronic myelogenous leukemia (CML) diagnosed in chronic phase (CP). BCR-ABL1 signaling is believed to be the driving force in CML pathogenesis, leading to disease progression and secondary genetic changes. Continuous BCRABL1 activity induces DNA damage and inhibits DNA repair, leading to genetic instability and clonal evolution [1,2]. Clonal evolution, manifested by cytogenetics and mutational changes, occurs in 510% of patients diagnosed in chronic phase, approximately 30% of patients in accelerated phase (AP), and 5080% of patients in blast phase (BP) [2,3]. A recent study demonstrated that the pattern of cytogenetic changes during clonal evolution remains similar in CML patients treated with or without tyrosine kinase inhibitors (TKIs), supporting the idea of genetic instability induced by BCR-ABL1 as the mechanism of clonal evolution[4]. The most common chromosomal aberrations during clonal evolution are unbalanced chromosomal changes, including + Ph, +8, i(17)(q10), and +19 [4], which are the so-called major route abnormalities. Reciprocal translocations are much less common and represent minor route abnormalities. Several rearrangements typically occurring in de novo acute myeloid leukemia (AML) and conferring prognostic value, such as inv(3)(q21q26)/t(3;3)(q21;q26), t(8;21) (q22,q22), t(15;17)(q22;q21), and inv(16)(p13q22), have been infrequently observed as secondary cytogenetic changes during clonal evolution of CML. Reciprocal rearrangements involving 11q23 are extremely rare in CML and until now only about ten cases in the form of single case reports are available in the literature [5-14]. The clinicopathological characteristics and prognostic value of 11q23 translocations in CML have not been studied systematically. Rearrangements involving 11q23/MLL locus are frequently encountered in acute leukemia. About 70%80% of infant acute leukemia has 11q23/MLL abnormalities, (...truncated)


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Wei Wang, Guilin Tang, Jorge E Cortes, Hui Liu, Di Ai, C Yin, Shaoying Li, Joseph D Khoury, Carlos Bueso-Ramos, L Medeiros, Shimin Hu. Chromosomal rearrangement involving 11q23 locus in chronic myelogenous leukemia: a rare phenomenon frequently associated with disease progression and poor prognosis, Journal of Hematology & Oncology, 2015, pp. 32, 8, DOI: 10.1186/s13045-015-0128-2