Genomic analysis of hairy cell leukemia identifies novel recurrent genetic alterations

Durham, Benjamin H.; Getta, Bartlomiej; Dietrich, Sascha; Taylor, Justin; Won, Helen; Bogenberger, James M; Scott, Sasynia N; Kim, Eun‐Hee; Chung, Young Rock; Chung, Stephen S.; Hüllein, Jennifer; Walther, Tatjana; Wang, Lu; Lu, Sydney X.; Oakes, Christopher C.; Tibes, Raoul; Haferlach, Torsten; Taylor, Barry S.; Tallman, Martin S.; Berger, Michael F.; Park, Jae H.; Zenz, Thorsten; Abdel‐Wahab, Omar

doi:10.1182/blood-2017-01-765107

Cited by 98 publications

(131 citation statements)

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“…Alterations of the cell cycle are essential in the pathology. In addition to the overexpression of cyclin D1, recurrent inactivation of the cell cycle inhibitor CDKN1B/p27 was identified in more than 10% of cases . Although TP53 mutations and/or del(17p) seem infrequent in HCL, it is recommended to assess TP53 status in case of PNA resistance .…”

Section: What Has Recently Improved Understanding Of Hairy Cell Leukementioning

confidence: 99%

“…In addition to the overexpression of cyclin D1, recurrent inactivation of the cell cycle inhibitor CDKN1B/p27 was identified in more than 10% of cases . Although TP53 mutations and/or del(17p) seem infrequent in HCL, it is recommended to assess TP53 status in case of PNA resistance . Inactivating KLF2 mutations were observed in 15% of HCL cases and 30% of marginal zone lymphomas (MZL) KLF2 is a transcription factor controlling the differentiation of multiple B‐cell subpopulations, including marginal zone B cells.…”

Section: What Has Recently Improved Understanding Of Hairy Cell Leukementioning

confidence: 99%

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Hairy cell leukemia: 2020 update on diagnosis, risk stratification, and treatment

2019

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Disease overview: Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders. They are characterized by the identification of hairy cells, a specific genetic profile, a different clinical course and the need for appropriate treatment. Diagnosis: Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of three or four based on the CD11C, CD103, CD123, and CD25 expression. Also, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation. Risk stratification: Progression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood and the immunoglobulin heavy chain variable region gene mutational status. The VH4-34 positive HCL cases are associated with poor prognosis. Treatment: Risk adapted therapy with purine nucleoside analogs (PNA) are indicated in symptomatic first line HCL patients. The use of PNA followed by rituximab represents an alternative option. Management of progressive or refractory disease is based on the use of BRAF inhibitors associated or not with MEK inhibitors, recombinant immunoconjugates targeting CD22 or BCR inhibitors.

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Section: What Has Recently Improved Understanding Of Hairy Cell Leukementioning

confidence: 99%

Section: What Has Recently Improved Understanding Of Hairy Cell Leukementioning

confidence: 99%

Hairy cell leukemia: 2020 update on diagnosis, risk stratification, and treatment

2019

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“…We reported that HCL expressing unmutated (>98% homology to germline) immunoglobulin heavy-chain variable (IGHV) rearrangement type IGHV4-34 expresses wild-type BRAF and has a poor prognosis like HCLv, whether immunophenotypically consistent with HCLv or HCL [12,13]. Mutations within MAP2K1 encoding MEK1 have been found in HCLv and IGHV4-34+ HCL [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Expression of the muscle-associated gene MYF6 in hairy cell leukemia

et al. 2020

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Hairy cell leukemia (HCL) is a purine analog-responsive B-cell malignancy containing the BRAF V600E mutation, expressing CD22, CD11c, CD103, tartrate resistant acid phosphatase (TRAP) CD25, CD123, and annexin 1A. BRAF V600E and the latter 4 markers are usually absent in the more aggressive and chemoresistant variant HCLv. To evaluate differences between HCL and HCLv, expression microarrays comparing HCL with HCLv were performed for 24694 genes using 47323 probes. Microarray data from 35 HCL and 27 HCLv purified samples showed the greatest HCL-HCLv difference in the muscle-associated gene MYF6, expressed by its 2 probes 18.5-and 10.8-fold higher in HCL than HCLv (p<0.0001). By real-time quantitative PCR (RQ-PCR), 100% of 152 classic HCL samples were MYF6positive, vs 5 (6%) of 90 blood donors. MYF6-expression was also detected in 18 (35%) of 51 with HCLv, 11 (92%) of 12 with HCL expressing unmutated IGHV4-34, 35 (73%) of 48 with chronic lymphocytic leukemia (CLL), and 1 (8%) of 12 with mantle cell lymphoma. Hypomethylation status of MYF6 supported expression in HCL more than HCLv. Posttreatment blood samples becoming negative by flow cytometry remained MYF6+ by RQ-PCR in 42 (48%) of 87 HCL patients, and MYF6 RQ-PCR could detect 1 HCL in 10 5 normal cells. MYF6, universally expressed in HCL and in most CLL samples, may be a useful biomarker for these leukemias. Further studies are underway to determine the role of MYF6 in HCL.

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“…In contrast to HCL, CCND3 mutations were identified in 13% of HCL‐V cases,23 a frequency that is identical to that observed in SMZL and less than the 25% of SDRPL cases 24, 26…”

Section: What Has Recently Improved the Understanding Of Hcl And Hcl‐mentioning

confidence: 74%

Hairy cell leukemia 2018: Update on diagnosis, risk‐stratification, and treatment

Troussard

Cornet

2017

American J Hematol

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Disease overviewHairy cell leukemia (HCL) and HCL‐like disorders, including HCL variant (HCL‐V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B‐cell disorders, characterized by the identification of hairy cells, a specific genetic profile, a different clinical course and the need for appropriate treatment.DiagnosisDiagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11C, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation.Risk stratificationProgression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood and the immunoglobulin heavy chain variable region gene mutational status. VH4‐34 positive HCL cases are associated with poor prognosisRisk adapted therapyPurine analogs (PNA) are indicated in symptomatic first line HCL patients. The use of PNA followed by rituximab represents an alternative option.Management of progressive or refractory diseaseIt is based on the use of BRAF inhibitors associated or not with MEK inhibitors, recombinant immunoconjugates targeting CD22 or BCR inhibitors.

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Genomic analysis of hairy cell leukemia identifies novel recurrent genetic alterations

Cited by 98 publications

References 28 publications

Hairy cell leukemia: 2020 update on diagnosis, risk stratification, and treatment

Hairy cell leukemia: 2020 update on diagnosis, risk stratification, and treatment

Expression of the muscle-associated gene MYF6 in hairy cell leukemia

Hairy cell leukemia 2018: Update on diagnosis, risk‐stratification, and treatment

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