New generation sequencing of targeted genes in the classical and the variant form of hairy cell leukemia highlights mutations in epigenetic regulation genes

Maître, Elsa; Bertrand, Philìppe; Maingonnat, Catherine; Viailly, Pierre-Julien; Wiber, Margaux; Naguib, Dina; Salaün, Véronique; Cornet, Édouard; Damaj, Gandhi; Sola, Brigitte; Jardin, Fabrice; Troussard, Xavier

doi:10.18632/oncotarget.25601

Cited by 44 publications

(57 citation statements)

References 52 publications

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“…In those patients, the possibility of mutation in exon 11 (F468C, D449E) should be excluded . In case of wild type BRAF gene, mutations in MAP2K1 encoding MEK (downstream protein of B‐RAF) were found in more than half of the cases . The MAP2K1 mutations also activate the MAPK pathway.…”

Section: What Has Recently Improved Understanding Of Hairy Cell Leukementioning

confidence: 99%

“…Sequencing of sequential samples at diagnosis and relapse, demonstrated the emergence of new mutations at relapse . Alterations of the cell cycle are essential in the pathology.…”

Section: What Has Recently Improved Understanding Of Hairy Cell Leukementioning

confidence: 99%

“…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%

“…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. Mutations of the genes of the epigenetic regulation genes were frequently observed, with mutations in the histone methyltransferase KMT2C (MLL3) occurring in 15% of patients .…”

Section: What Has Recently Improved Understanding Of Hairy Cell Leukementioning

confidence: 99%

“…And. more rarely mutations in histone demethylase KDM6A or histone acetyltransferase CREBBP ( CBP ) . Others mutations in the chromatin remodeling complex family ARID1A, ARID1B were also described.…”

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%

“…Sequencing of sequential samples at diagnosis and relapse, demonstrated the emergence of new mutations at relapse . Alterations of the cell cycle are essential in the pathology.…”

Section: What Has Recently Improved Understanding Of Hairy Cell Leukementioning

confidence: 99%

Section: What Has Recently Improved Understanding Of Hairy Cell Leukementioning

confidence: 99%

Section: What Has Recently Improved Understanding Of Hairy Cell Leukementioning

confidence: 99%

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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Hairy cell leukemia 2022: Update on diagnosis, risk‐stratification, and treatment

2021

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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 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 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 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. VH4-34-positive HCL cases are associated with a poor prognosis. Treatment: Patients should be treated only if HCL is symptomatic. Chemotherapy with risk adapted therapy purine analogs (PNAs) are indicated in first-line HCL patients. The use of chemo-immunotherapy combining PNAs and rituximab (R) represents an increasingly used therapeutic approach. Management of relapsed/ refractory disease is based on the use of BRAF inhibitors (BRAFi) plus rituximab or MEK inhibitors (MEKi), recombinant immunoconjugates targeting CD22 or BrutonTyrosine Kinase inhibitors (BTKi). However, the optimal sequence of the different treatments remains to be determined. The Bcl2-inhibitors (Bcl-2i) can play a major role in the future. | INTRODUCTIONHairy cell leukemia (HCL) is recognized as an entity by the World Health Organization since 2008 1 and in the last 2017 revision of the WHO classification of lymphoid neoplasms. 2 HCL, four to five times more frequent in men than women, accounts for 2% of all leukemias with approximately 1.100 new HCL cases in the United States. 3 The few available population-based studies are limited. [4][5][6][7][8] When including HCL and HCL-like disorders, the overall age-adjusted to the 2000 US population incidence rate is 0.7 per 100 000 in men and 0.3/100 000 in women. When adjusting to the worldwide population, the incidence rate of HCL is 0.3 and 0.1/100 000, respectively, and remains relatively stable over time. 8 It is lower in non-Hispanic/black, Hispanic, or Asian/pacific Islander. Despite an improvement of overall (OS) and relative survival (RS), a significantly lower OS is observed among African American individuals compared with other ethnic groups. 6 The mortality rates for patients with HCL is similar to those of the general population 5 years after diagnosis. 9 HCL must be differentiated from other

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Hairy cell leukemia 2024: Update on diagnosis, risk‐stratification, and treatment—Annual updates in hematological malignancies

Troussard,

Maître,

Paillassa

2024

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 heterogenous 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 bone marrow infiltration and the presence of BRAFV600E 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 a poor prognosis, as well as HCL with TP53 mutations and HCL‐V.TreatmentPatients should be treated only if HCL is symptomatic. Chemotherapy with risk‐adapted therapy purine analogs (PNAs) are indicated in first‐line HCL patients. The use of chemo‐immunotherapy combining cladribine (CDA) and rituximab (R) represents an increasingly used therapeutic approach. Management of relapsed/refractory disease is based on the use of BRAF inhibitors (BRAFi) plus R, MEK inhibitors (MEKi), recombinant immunoconjugates targeting CD22, Bruton tyrosine kinase inhibitors (BTKi), and Bcl‐2 inhibitors (Bcl‐2i). However, the optimal sequence of the different treatments remains to be determined.

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New generation sequencing of targeted genes in the classical and the variant form of hairy cell leukemia highlights mutations in epigenetic regulation genes

Cited by 44 publications

References 52 publications

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

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

Hairy cell leukemia 2022: Update on diagnosis, risk‐stratification, and treatment

Hairy cell leukemia 2024: Update on diagnosis, risk‐stratification, and treatment—Annual updates in hematological malignancies

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