Complex Patterns of Chromosome 11 Aberrations in Myeloid Malignancies Target CBL, MLL, DDB1 and LMO2

Klampfl, Thorsten; Milosevic, Jelena D.; Puda, Ana; Schönegger, Andreas; Bagienski, Klaudia; Berg, Tiina; Harutyunyan, Ashot S.; Gisslinger, Bettina; Rumi, Elisa; Malcovati, Luca; Pietra, Daniela; Elena, Chiara; Porta, Matteo Giovanni Della; Pieri, Lisa; Guglielmelli, Paola; Bock, Christoph; Doubek, Michael; Dvořáková, Dana; Suvajdžić, Nada; Tomin, Dragica; Tos̆ić, Nataša; Ráčil, Zdeněk; Steurer, Michael; Pavlović, Sonja; Vannucchi, Alessandro M.; Cazzola, Mario; Gisslinger, Heinz; Královics, Róbert

doi:10.1371/journal.pone.0077819

Cited by 13 publications

(12 citation statements)

References 45 publications

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“…In CML, alterations involving 11q23 and affecting MLL are rare, and have been reported only sporadically (15)(16)(17)(18)(19). However, this translocation could affect other genes such as CBL, generating a new chimeric gene that could deregulate the cell cycle and affect the treatment response (20,21).…”

Section: Discussionmentioning

confidence: 99%

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

Gutierrez

Noriega

Laudicina³

et al. 2017

Oncology Letters

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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...

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Section: Discussionmentioning

confidence: 99%

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

Gutierrez

Noriega

Laudicina³

et al. 2017

Oncology Letters

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“…In AML, chromosome 11 is one of the most common targets of gene amplification [8]. Amplicons on chromosome 11 may vary in size, but they usually involve the long arm of the chromosome, particularly the region 11q23, where an MLL proto-oncogene (myeloid/lymphoid leukemia or mixed-lineage leukemia (trithorax homolog [,]Drosophila)) is located [9]. In BC, nonrandom abnormalities of chromosome 11 are frequently reported, with involvement of 11p15, 11q13, and 11q23 [6].…”

Section: Discussionmentioning

confidence: 99%

Appropriate Clinical Strategies for Breast Cancer Coexisting with Acute Myeloid Leukemia in the Genomic-Molecular Era: A Case Report

Mallik

Yang

et al. 2016

Breast Care

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Background: The coexistence of breast cancer (BC) and acute myeloid leukemia (AML) has rarely been reported. Considering the fatality of AML, the management of this condition is based on treating the AML immediately while putting BC treatment on hold. Case Report: Here, we report a synchronous occurrence of BC and AML. Prognostic factors for both BC and AML were determined by genomic and molecular evaluation. The evaluation for AML showed a relatively good prognosis, and we simultaneously conducted treatment for AML and BC. The patient has survived for more than 3 years, which makes this the case with the longest survival reported. Conclusion: In patients with BC and AML, it is essential to determine the prognosis through a genomic and molecular evaluation. For a certain group of patients whose prognosis of AML is good, simultaneous or initial treatment of BC before treatment of AML may be appropriate.

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“…Most chromosome 11 aberrations are related to non-ATM genes, such as the MLL gene (18). There are few reports of AML in ataxia telangiectasia patients, and the somatic inactivation of the ATM gene in AML patients has not yet been reported to date (19)(20)(21).…”

Section: Discussionmentioning

confidence: 99%

Acute Megakaryoblastic Leukemia with Myelodysplasia-related Changes Associated with ATM Gene Deletion

et al. 2016

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Ataxia telangiectasia mutated (ATM) is a tumor suppressor gene, and its somatic inactivation plays a role in the pathogenesis of lymphoid malignancies. However, the role of ATM in patients with myeloid malignancies is still unknown. We herein report a case of acute megakaryoblastic leukemia (AMKL) with ATM gene deletion. An 84-year-old Japanese woman presenting with a pale face and pancytopenia was admitted to our institution and diagnosed to have AMKL with ATM gene deletion. She was treated with intravenous azacitidine. The azacitidine treatment was effective for approximately 1 year. Somatic inactivation of the ATM gene may therefore be involved in the pathogenesis of AMKL.

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Complex Patterns of Chromosome 11 Aberrations in Myeloid Malignancies Target CBL, MLL, DDB1 and LMO2

Cited by 13 publications

References 45 publications

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

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

Appropriate Clinical Strategies for Breast Cancer Coexisting with Acute Myeloid Leukemia in the Genomic-Molecular Era: A Case Report

Acute Megakaryoblastic Leukemia with Myelodysplasia-related Changes Associated with ATM Gene Deletion

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