Complex and cryptic chromosomal rearrangements involving the MLL gene in acute leukemia: A study of 7 patients and review of the literature

Braekeleer, Étienne De; Meyer, Claus; Douet‐Guilbert, Nathalie; Morel, Frédéric; Bris, Marie‐Josée Le; Berthou, Christian; Arnulf, Bertrand; Marschalek, Rolf; Férec, Claude; Braekeleer, Marc De

doi:10.1016/j.bcmd.2010.02.011

Cited by 29 publications

(28 citation statements)

References 62 publications

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“…Genetic alterations in 11q23 are frequent in hematological malignancies, particularly in acute leukemia (6). These alterations affect the MLL gene in ~85% of cases and are associated with an adverse prognosis (14).…”

Section: Discussionmentioning

confidence: 99%

“…This deletion was confirmed by molecular analysis of the reciprocal transcript ABL1-BCR (data not shown). Deletions on der (9) have been reported in several studies in association with a bad response prior to the TKI era (6,11,23).…”

Section: Discussionmentioning

confidence: 99%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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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%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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“…Note 36 cases are available to date (Kaneko et al,1986;Gregoire et al, 1987;Selypes and Laszlo, 1987;Hagemeijer et al, 1987;Hayashi et al, 1989;Raimondi et al, 1989;Shippey et al, 1989;Pui et al, 1990;Lampert et al, 1991;Abshire et al, 1992;Bernard et al, 1994;Felix et al, 1995;Felix et al, 1998;Harrison et al, 1998;Laughlin et al, 1998;Pinto et al, 1998;Secker-Walker et al, 1998;Nakamura et al, 2000;von Bergh et al, 2000;Chessells et al, 2002;Kim et al, 2002;Tsujioka et al, 2003;Douet-Guilbert et al, 2005;Sagawa et al, 2006;Jeon and Yi, 2009;de Braekeleer et al, 2010;Shinohara et al, 2010); we have excluded from this review a case of t(1;6;11)(p32;q21;q23) in a T-cell lymphoma referred as "T-CLL", as it probably represents another entity (Mecucci et al, 1988). We must also keep in mind that some of the t(1;11)(p32;q23) above harvested may not all share the common genetic event 5' MLL -3' EPS15: a case of t(1;11)(p32;q23), del(5q), +8 in a patient with therapyrelated leukaemia has recently been described without MLL rearrangement (Yamamoto et al, 2010).…”

Section: Diseasementioning

confidence: 99%

“…There was two complex (three way) translocations: a t(1;11;4)(p32;q23q13;p16) and a t(1;11;10)(p32;q23;q24) (Selypes and Laszlo, 1987;de Braekeleer et al, 2010).…”

Section: Cytogenetics Morphologicalmentioning

confidence: 99%

t(1;11)(p32;q23)

Huret¹

2011

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Characterization of chromosome 11 breakpoints and the areas of deletion and amplification in patients with newly diagnosed acute myeloid leukemia

Sarova

Březinová

Zemanová

et al. 2013

Genes Chromosomes & Cancer

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Chromosome 11 abnormalities are found in many hematological malignancies. In acute myeloid leukemia (AML), a proto-oncogene MLL (11q23.3) is frequently altered. However, rearrangements involving other regions of chromosome 11 have been reported. Therefore, we have characterized the chromosome 11 breakpoints and common deleted and amplified areas in the bone marrow or peripheral blood cells of newly diagnosed patients with AML. Using molecular-cytogenetic methods (multicolor fluorescence in situ hybridization (mFISH), multicolor banding (mBAND), microarrays, and FISH with bacterial artificial chromosome (BAC) probes, chromosome 11 abnormalities were delineated in 54 out of 300 (18%) newly diagnosed AML patients. At least 36 different chromosome 11 breakpoints were identified; two were recurrent (11p15.4 in the NUP98 gene and 11q23.3 in the MLL gene), and three were possibly nonrandom: 11p13 (ch11:29.31-31.80 Mb), 11p12 (ch11:36.75-37.49 Mb) and 11q13.2 (68.31-68.52 Mb). One new MLL gene rearrangement is also described. No commonly deleted region of chromosome 11 was identified. However, some regions were affected more often: 11pter-11p15.5 (n = 4; ch11:0-3.52 Mb), 11p14.1-11p13 (n = 4; ch11:28.00-31.00 Mb) and 11p13 (n = 4; ch11:31.00-31.50 Mb). One commonly duplicated (3 copies) region was identified in chromosomal band 11q23.3-11q24 (n = 9; ch11:118.35-125.00 Mb). In all eight cases of 11q amplification (>3 copies), only the 5' part of the MLL gene was affected. This study highlights several chromosome 11 loci that might be important for the leukemogeneic process in AML.

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Complex and cryptic chromosomal rearrangements involving the MLL gene in acute leukemia: A study of 7 patients and review of the literature

Cited by 29 publications

References 62 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

t(1;11)(p32;q23)

Characterization of chromosome 11 breakpoints and the areas of deletion and amplification in patients with newly diagnosed acute myeloid leukemia

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