An unusual translocation, t(1;11)(q21;q23), in a case of chronic myeloid leukemia with a cryptic Philadelphia chromosome

Abstract

Abstract. Chronic myeloid leukemia (CML) is characterized by the translocation t(9;22)(q34;q11) [Philadelphia (Ph) chromosome). Although not frequently occurring, additional chromosome abnormalities (ACAs) can be detected at diagnosis and a number have been associated with an adverse cytogenetic and molecular outcome. The present study reports a case of CML presenting with the translocation t(1;11)(q21;q23) and a cryptic Ph chromosome. The presence of ACAs could generate greater genetic instability, promoting the emergence of further alterations. The present findings suggest that t(1;11) (q21;q23) can prevent a good response to tyrosine kinase inhibitor (TKI) therapy developing a primary resistance. In the present patient, at a recent follow-up, the T315I mutation was detected. This mutation confers full resistance to all available TKI, except ponatinib, which was not a therapeutic option due to comorbidities. IntroductionChronic myeloid leukemia (CML) is a clonal disease of pluripotent hematopoietic stem cells that is characterized by the Philadelphia (Ph) chromosome with the reciprocal translocation t(9;22)(q34;q11). At diagnosis, the majority of cases (85%) exhibit the typical Ph chromosome as the only cytogenetic finding. A few cases either harbor variant translocations [t(v;22)] or cryptic rearrangement (1).However, additional chromosome abnormalities (ACAs) are a recurring event associated with clonal evolution. An extra Ph, +8, i(17q) and +19 have been described as the most common secondary changes (known as the major route), whereas others infrequent changes have been labeled as the minor route. The major route of ACAs is usually detected during disease progression into the accelerated phase or blast crisis (2). At diagnosis, this has been documented with low frequency (<5% of cases) (3). These aberrations have been reported as an independent prognostic factor with a negative impact on the cytogenetic and molecular response (4,5). The t(1;11)(q21;q23) translocation has been described at diagnosis in certain cases of pediatric acute myeloid leukemia or myelomonocytic leukemia, with a poor prognosis, but the subgroup with this rearrangement suggests an uncertain impact in the outcome of acute leukemia (6).The present study reports a rare case of CML with a cryptic Ph chromosome and a t(1;11)(q21;q23) translocation at diagnosis, with unfavourable responses, even though the patient received appropriate treatments. Furthermore, a T315I mutation was later detected in the patient. Case reportIn June 2000, a 47-year-old female with a CML diagnosis was referred to the Hematology Research Institute 'Mariano R. Castex', National Academy of Medicine (Buenos Aires, Argentina) for further studies and treatment. The clinical records of the patient indicated the onset of the disease in 1998, when the patient was 45 years old, with a cytogenetic study showing the translocation t(1;11)(q21;q23). The patient was treated with hydroxyurea (1 g/day).In the first consultation at the current institute, the patient presented wit...

Inhibition of eukaryotic initiation factor 3B suppresses proliferation and promotes apoptosis of chronic myeloid leukemia cells

“…Chronic myeloid leukemia (CML) is a hematopoietic stem cell (HSC) malignancy that results from the formation of the Philadelphia chromosome due to reciprocal chromosomal translocation t(9;22)(q34.12;q11.23), and it accounts for 15-20% of all leukemias. 1 Patients with CML need to be treated for life; moreover, the prognosis of patients with blastic transformation of CML is extremely poor. Thus, there is an unmet need to find better treatments for CML.…”

Coexistence of recurrent chromosomal abnormalities and the Philadelphia chromosome in acute and chronic myeloid leukemias: report of five cases and review of literature

“…CML with the t(9;22) translocation rarely incurs the additional t(9;11) during disease progression. In the last twenty years, no more than 5 cases have been reported in the literature [ 12 – 14 ], and none have been reported in China. Our study found that the proportion of patients with t(9;22) accompanied by the t(9;11) translocation was even lower 0.14% (2/1382).…”

Coexistence of Recurrent Chromosomal Abnormalities and the Philadelphia Chromosome in Acute and Chronic Myeloid Leukemias: Report of Five Cases and Review of Literature

“…CML with the t(9;22) translocation rarely incurs the additional t(9;11) during disease progression. To date, no more than 5 cases have been reported in the literature [12,13,14], and none have been reported in China. Our study found that the proportion of patients with t(9;22) accompanied by the t(9;11) translocation was even lower 0.14% (2/1382).…”