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

Abstract

BackgroundProgression 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.MethodsWe 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.ResultsA 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.ConclusionsIn 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.

Clinical and prognostic significance of 3q26.2 and other chromosome 3 abnormalities in CML in the era of tyrosine kinase inhibitors

“…Indeed, we recently showed that 11q23/MLL rearrangement, a rare minor route cytogenetic change in CML, is associated with poor prognosis. 40 In the current study, we found that 3q26.2 aberration, although regarded as a minor route change, confers a worse prognosis than other ACAs, including trisomy 8, 1 of major route changes. In addition, the concurrent presence of other chromosomal changes in cases with 3q26.2 rearrangements did not affect the survival (Figure 5), indicating the predominant role of 3q26.2 in determining prognosis in these cases.…”

Prognostic significance of additional chromosomal abnormalities at the time of diagnosis in patients with chronic myeloid leukemia treated with frontline tyrosine kinase inhibitors

“…For instance, chromosome 17, chromosome 3, and complex cytogenetic abnormalities have been associated with worse outcomes, while other abnormalities like deletion of derivative 9 have been shown to have no impact on prognosis when subjected to TKI therapy . Thus, the minor route ACA are not an entirely homogenous group with certain changes such as those involving 11q23 and 3q26 associated with TKI resistance and inferior outcomes . Wang and colleagues proposed a new classification system accounting for the impact of these abnormalities …”

Myeloid neoplasms with concurrent BCR‐ABL1 and CBFB rearrangements: A series of 10 cases of a clinically aggressive neoplasm

“…The occurrence of additional cytogenetic alterations other than t(9;22) is observed in up to 80% of cases of CML‐BP . The most common additional cytogenetic abnormalities include trisomy 8, an extra copy of the Ph chromosome, 3q26 rearrangements, monosomy 7/del(7q), i(17)(q10), trisomy 21, minus Y, and trisomy 19 …”