Detection of an IGH-<i>BRAF</i> fusion in a patient with BRAF Val600Glu negative hairy cell leukemia

Thompson, Ella R.; Lim, Kenneth; Kuzich, James A.; McBean, Michelle; Westerman, David; Tam, Constantine S.; Blombery, Piers

doi:10.1080/10428194.2020.1753045

Cited by 6 publications

(5 citation statements)

References 15 publications

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“…However, the frequency of the BRAF V600E mutation differed according to the studies, ranging from 80% to 100% [4,21]. Some alternative BRAF mutations were also reported in exon 11 [27] as well as a IGH/BRAF fusion leading to BRAF upregulation [28]. Consistent with the literature, we found the BRAF V600E mutation in 93% (76/82 pts).…”

Section: Discussionsupporting

confidence: 87%

Deciphering Genetic Alterations of Hairy Cell Leukemia and Hairy Cell Leukemia-like Disorders in 98 Patients

Maître

Tomowiak²,

Lebecque

et al. 2022

Cancers

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Hairy cell leukemia (cHCL) patients have, in most cases, a specific clinical and biological presentation with splenomegaly, anemia, leukopenia, neutropenia, monocytopenia and/or thrombocytopenia, identification of hairy cells that express CD103, CD123, CD25, CD11c and identification of the V600E mutation in the B-Raf proto-oncogene (BRAF) in 90% of cases. Monocytopenia is absent in vHCL and SDRPL patients and the abnormal cells do not express CD25 or CD123 and do not present the BRAFV600E mutation. Ten percent of cHCL patients are BRAFWT and the distinction between cHCL and HCL-like disorders including the variant form of HCL (vHCL) and splenic diffuse red pulp lymphoma (SDRPL) can be challenging. We performed deep sequencing in a large cohort of 84 cHCL and 16 HCL-like disorders to improve insights into the pathogenesis of the diseases. BRAF mutations were detected in 76/82 patients of cHCL (93%) and additional mutations were identified in Krüppel-like Factor 2 (KLF2) in 19 patients (23%) or CDKN1B in 6 patients (7.5%). Some KLF2 genetic alterations were localized on the cytidine deaminase (AID) consensus motif, suggesting AID-induced mutations. When analyzing sequential samples, a clonal evolution was identified in half of the cHCL patients (6/12 pts). Among the 16 patients with HCL-like disorders, we observed an enrichment of MAP2K1 mutations in vHCL/SDRPL (3/5 pts) and genes involved in the epigenetic regulation (KDM6A, EZH2, CREBBP, ARID1A) (3/5 pts). Furthermore, MAP2K1 mutations were associated with a bad prognosis and a shorter time to next treatment (TTNT) and progression-free survival (PFS), independently of the HCL classification.

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Section: Discussionsupporting

confidence: 87%

Deciphering Genetic Alterations of Hairy Cell Leukemia and Hairy Cell Leukemia-like Disorders in 98 Patients

Maître

Tomowiak²,

Lebecque

et al. 2022

Cancers

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“…The BRAF V600E mutation is the main activation mechanism of the MAP kinase signaling pathway. However, two HCL patients were documented with t(7;14)(q34;q32) and IGH‐BRAF fusion gene without BRAF V600E mutation, suggesting that the fusion mechanism could be a rare way to activate the MEK–ERK pathway 67,68 …”

Section: What Has Recently Improved Our Understanding Of Hcl?mentioning

confidence: 99%

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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“…6 They also present the BRAF CR3 kinase domain without Germinal centre B cells differentiate into plasma cells or memory cells. Chromosomal translocations are frequently observed in myeloma, a plasma cell tumour, whereas translocations are extremely rare in classical HCL (Table 1), [10][11][12] which is of memory cell origin. The haematopoietic stem cells in HCL harbour the BRAF mutations, and BRAF mutations are also found in a percentage of myeloma cells.…”

Section: Hairy Cell Leukaemia With An Igh-braf Fusion Genementioning

confidence: 99%

Hairy cell leukaemia with an IGH–BRAF fusion gene

et al. 2023

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Detection of an IGH-BRAF fusion in a patient with BRAF Val600Glu negative hairy cell leukemia

Cited by 6 publications

References 15 publications

Deciphering Genetic Alterations of Hairy Cell Leukemia and Hairy Cell Leukemia-like Disorders in 98 Patients

Deciphering Genetic Alterations of Hairy Cell Leukemia and Hairy Cell Leukemia-like Disorders in 98 Patients

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

Hairy cell leukaemia with an IGH–BRAF fusion gene

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