Gain of the short arm of chromosome 2 (2p gain) has a significant role in drug‐resistant chronic lymphocytic leukemia

Kostopoulou, F.; Gabillaud, Clémentine; Chapiro, Élise; Grange, Béatrice; Tran, Julie; Bouzy, Simon; Degaud, Michaël; Ghamlouch, Hussein; Garff‐Tavernier, Magali Le; Maloum, Karim; Choquet, Sylvain; Leblond, Véronique; Gabarre, Jean; Lavaud, Anne; Morel, Véronique; Roos‐Weil, Damien; Uzunov, Madalina; Guièze, Romain; Bernard, Olivier; Susín, Santos A.; Tournilhac, Olivier; Nguyen‐Khac, Florence

doi:10.1002/cam4.2123

Cited by 10 publications

(6 citation statements)

References 24 publications

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“…Moreover, aberrations with potential clinical significance such as deletion of 6q21, gain of 2p, recurrent translocations [e.g. t(14;19)] or complex karyotypes (CK) are visible with CBA but not detected with the standard CLL FISH analysis 12–15 . Thus, performing CBA in combination with interphase FISH results in a more comprehensive genetic characterization of CLL.…”

Section: Cytogenetic Analysis In Chronic Lymphocytic Leukemia: a Hist...mentioning

confidence: 99%

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Cytogenetics in Chronic Lymphocytic Leukemia: ERIC Perspectives and Recommendations

et al. 2022

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Mounting evidence underscores the clinical value of cytogenetic analysis in chronic lymphocytic leukemia (CLL), particularly as it allows the identification of complex karyotype, that has recently emerged as a prognostic and potentially predictive biomarker. That said, explicit recommendations regarding the methodology and clinical interpretation of either chromosome banding analysis (CBA) or chromosome microarray analysis (CMA) are still lacking. We herein present the consensus of the Cytogenetic Steering Scientific Committee of ERIC, the European Research Initiative on CLL, regarding methodological issues as well as clinical interpretation of CBA/CMA and discuss their relevance in CLL. ERIC considers CBA standardized and feasible for CLL on the condition that standards are met, extending from the use of novel mitogens to the accurate interpretation of the findings. On the other hand, CMA, is also standardized, however, robust data on its clinical utility are still scarce. In conclusion, cytogenetic analysis is not yet mature enough to guide treatment choices in CLL. That notwithstanding, ERIC encourages the wide application of CBA, and potentially also CMA, in clinical trials in order to obtain robust evidence regarding the predictive value of specific cytogenetic profiles towards refining risk stratification and improving the management of patients with CLL.

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Section: Cytogenetic Analysis In Chronic Lymphocytic Leukemia: a Hist...mentioning

confidence: 99%

“…t (14;19)] or complex karyotypes (CK) are visible with CBA but not detected with the standard CLL FISH analysis. [12][13][14][15] Thus, performing CBA in combination with interphase FISH results in a more comprehensive genetic characterization of CLL.…”

mentioning

confidence: 99%

Cytogenetics in Chronic Lymphocytic Leukemia: ERIC Perspectives and Recommendations

et al. 2022

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“…CBA and interphase FISH are complementary techniques (94). More specifically, CBA can detect abnormalities that cannot be found by a limited panel of FISH probes and FISH can detect abnormalities that cannot be found by CBA due to an inherently lower resolution (95)(96)(97)(98). As such, performing CBA in combination with interphase FISH results in a more sensitive measurement of CK.…”

Section: Complex Karyotype/genomic Complexitymentioning

confidence: 99%

Treatment Approaches to Chronic Lymphocytic Leukemia With High-Risk Molecular Features

Straten¹,

Hengeveld²,

Kater³

et al. 2021

Front. Oncol.

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The clinical course of chronic lymphocytic leukemia (CLL) is highly variable. Over the past decades, several cytogenetic, immunogenetic and molecular features have emerged that identify patients suffering from CLL with high-risk molecular features. These biomarkers can clearly aid prognostication, but may also be capable of predicting the efficacy of various treatment strategies in subgroups of patients. In this narrative review, we discuss treatment approaches to CLL with high-risk molecular features. Specifically, we review and provide a comprehensive overview of clinical trials evaluating the efficacy of chemotherapy, chemoimmunotherapy and novel agent-based treatments in CLL patients with TP53 aberrations, deletion of the long arm of chromosome 11, complex karyotype, unmutated IGHV, B cell receptor stereotypy, and mutations in NOTCH1 or BIRC3. Furthermore, we discuss future pharmaceutical and immunotherapeutic perspectives for CLL with high-risk molecular features, focusing on agents currently under investigation in clinical trials.

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“…Across nearly all cancers, including those affecting children, adolescents, and young adults, XPO1 is expressed ( Figure 1 ) [ 52 , 53 , 54 , 55 , 56 , 57 , 58 ], and higher expression has been correlated with inferior outcome. XPO1 is located on chromosome arm 2p, a region frequently associated with somatic copy number changes in cancer (e.g., gastric cancer, CLL, lymphomas, neuroblastoma, and rhabdomyosarcoma), and a region that includes putative proto-oncogenes N-MYC , REL , and BCL11A [ 7 , 59 , 60 , 61 , 62 ]. This region may be key to understanding how XPO1 regulation is coopted to promote oncogenesis and to distinguish between sufficiency and necessity of overexpression to promote aggressive disease.…”

Section: Xpo1 Biological Function and Relevancementioning

confidence: 99%

Therapeutic Targeting of Exportin-1 in Childhood Cancer

Galinski

Alexander

Mitchell

et al. 2021

Cancers

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Overexpression of Exportin-1 (XPO1), a key regulator of nuclear-to-cytoplasmic transport, is associated with inferior patient outcomes across a range of adult malignancies. Targeting XPO1 with selinexor has demonstrated promising results in clinical trials, leading to FDA approval of its use for multiple relapsed/refractory cancers. However, XPO1 biology and selinexor sensitivity in childhood cancer is only recently being explored. In this review, we will focus on the differential biology of childhood and adult cancers as it relates to XPO1 and key cargo proteins. We will further explore the current state of pre-clinical and clinical development of XPO1 inhibitors in childhood cancers. Finally, we will outline potentially promising future therapeutic strategies for, as well as potential challenges to, integrating XPO1 inhibition to improve outcomes for children with cancer.

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Gain of the short arm of chromosome 2 (2p gain) has a significant role in drug‐resistant chronic lymphocytic leukemia

Cited by 10 publications

References 24 publications

Cytogenetics in Chronic Lymphocytic Leukemia: ERIC Perspectives and Recommendations

Cytogenetics in Chronic Lymphocytic Leukemia: ERIC Perspectives and Recommendations

Treatment Approaches to Chronic Lymphocytic Leukemia With High-Risk Molecular Features

Therapeutic Targeting of Exportin-1 in Childhood Cancer

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