BRAF mutations are very rare in B- and T-cell pediatric acute lymphoblastic leukemias

Davidsson, Josef; Lilljebjörn, Henrik; Panagopoulos, Ioannis; Fioretos, Thoas; Johansson, Bertil

doi:10.1038/leu.2008.14

Cited by 25 publications

(13 citation statements)

References 16 publications

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“…The BRAF V600E mutation has been previously found in a significant proportion of solid cancers [12][13][14] and in Langerhans cell histiocytosis, 15 whereas BRAF mutations other than V600E have been observed in small proportions of patients with acute lymphoblastic leukemia 16,17 or B-cell lymphomas. 18 The findings of this study indicate that the allele-specific PCR we developed is able to detect the BRAF V600E mutation in all patients with HCL.…”

Section: Resultsmentioning

confidence: 99%

The BRAF V600E mutation in hairy cell leukemia and other mature B-cell neoplasms

Arcaini¹,

Zibellini²,

Boveri

et al. 2012

Blood

157

122

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The somatically acquired V600E mutation of the BRAF gene has been recently described as a molecular marker of hairy cell leukemia (HCL). We developed an allele-specific PCR for this mutation and studied 62 patients with HCL, 1 with HCL variant, 91 with splenic marginal zone lymphoma, 29 with Waldenström macroglobulinemia, and 57 with B-cell chronic lymphoproliferative disorders. The BRAF V600E mutation was detected in all HCL cases and in only 2 of the remaining 178 patients. These 2 subjects had B-cell chronic lymphoproliferative disorders that did not fulfill the diagnostic criteria for HCL. Despite the positive PCR finding, the mutation could not be detected by Sanger sequencing in these 2 cases, suggesting that it was associated with a small subclone. We conclude that the BRAF V600E mutation is present in all patients with HCL and that, in combination with clinical and morphologic features, represents a reliable molecular marker for this condition.

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Section: Resultsmentioning

confidence: 99%

The BRAF V600E mutation in hairy cell leukemia and other mature B-cell neoplasms

Arcaini¹,

Zibellini²,

Boveri

et al. 2012

Blood

157

122

View full text Add to dashboard Cite

show abstract

“…Specificity was also assessed in 115 patients with non-HCL chronic B-cell neoplasms. Because absence 9 or very rare occurrence [13][14][15][16][17] of BRAF-V600E has been already reported in several B-cell tumors, we focused on HCL-like disorders that, being rare, have been so far poorly investigated. Therefore, we included, among the 115 cases, 79 patients with SMZL and SLLU, of which 65 previously unreported.…”

Section: Resultsmentioning

confidence: 99%

Simple genetic diagnosis of hairy cell leukemia by sensitive detection of the BRAF-V600E mutation

Tiacci

Schiavoni

Forconi

et al. 2012

Blood

174

131

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Hairy cell leukemia (HCL) is a distinct clinicopathologic entity that responds well to purine analogs but is sometimes difficult to differentiate from HCL-like disorders (eg, splenic marginal zone lymphoma and HCL variant). We recently identified the BRAF-V600E mutation as the disease-defining genetic event in HCL. In this study, we describe a new, simple, and inexpensive test for genetics-based diagnosis of HCL in whole-blood samples that detects BRAF-V600E through a sensitive allele-specific PCR qualitative assay followed by agarose-gel electrophoresis. IntroductionHairy cell leukemia (HCL) is a distinct entity usually characterized by splenomegaly (without lymphadenopathy), pancytopenia, and infiltration of BM, spleen, and liver by leukemic B cells with "hairy" appearance. In contrast to other chronic B-cell leukemias, HCL cells circulate at low percentages in the blood, 1 and exhibit distinct functional features and gene expression profile. 2,3 HCL diagnosis relies on morphologic and immunophenotypic criteria 1-4 that usually allow its distinction from HCL-like disorders of the 2008 World Health Organization classification, that is, splenic marginal zone lymphoma (SMZL) and splenic lymphoma/ leukemia unclassifiable (SLLU; including HCL variant [HCL-v]). 5 A correct diagnosis is critical because purine analogs (pentostatin and cladribine) are highly effective only in HCL. 4 The most problematic cases can be diagnosed using annexin-A1 immunostaining, 6-8 which we previously reported to be highly sensitive and specific for HCL among B-cell lymphomas. 6 However, because annexin-A1 is also expressed by myeloid and T cells, 6 this immunohistochemical staining may be difficult to interpret in BM biopsies with low percentages of HCL cells. Moreover, immunocytochemistry for annexin-A1 is not readily applicable to routine hematologic samples, such as peripheral blood or diluted BM aspirate (because of dry tap), that are also usually poor in HCL cells and rich in neutrophils and T cells.An ideal solution would be a sensitive and specific test for a genetics-based diagnosis of HCL. We recently identified BRAF-V600E as the HCL-defining genetic lesion (present in all HCL cases, absent in other B-cell neoplasms) 9 by Sanger sequencing of BRAF exon 15. However, this technique required Ն 30% leukemic cells for reliably detecting a clonal heterozygous mutation. Thus, the rare HCL cells typically present in the blood of most patients had to be purified through cell sorting, 9 a laborious procedure not amenable to a routine diagnostic setting.Aims of this study were: (1) to develop a sensitive, easy, and inexpensive test for the routine clinical diagnosis of HCL in blood samples, based on BRAF-V600E detection by allele-specific PCR (AS-PCR) followed by conventional agarose-gel electrophoresis; and (2) to assess the diagnostic accuracy of this test in a large cohort of HCL and HCL-like disorders. Methods Tumor samplesWe studied 117 HCL patients: 96 before therapy and 21 after therapy, all with detectable disease (at least 0.1% ...

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“…V600E) is observed broadly in solid cancers of multiple primary sites (59,60). Leukemias of lymphoid origin express B-Raf, and other than the recent discovery of hairy cell leukemia, mutations of the BRAF gene are very rare, suggesting a fundamental and conserved role in T cell leukemia and possibly normal T cell function (61)(62)(63)(64)(65)(66)(67). Although there are few studies that focus on the importance of B-Raf to T cell physiology, it has been shown that MAPK signaling during T cell development progression beyond the CD4-CD8 double positive stage requires B-Raf, and rescue experiments with B-Raf can restore proliferation through MAPK signaling in anergic T cells (40,67).…”

Section: Discussionmentioning

confidence: 99%

B-Raf Regulation of Integrin α4β1-mediated Resistance to Shear Stress through Changes in Cell Spreading and Cytoskeletal Association in T Cells

Brown

Khalili

Rodriguez-Cruz

et al. 2014

Journal of Biological Chemistry

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BRAF mutations are very rare in B- and T-cell pediatric acute lymphoblastic leukemias

Cited by 25 publications

References 16 publications

The BRAF V600E mutation in hairy cell leukemia and other mature B-cell neoplasms

The BRAF V600E mutation in hairy cell leukemia and other mature B-cell neoplasms

Simple genetic diagnosis of hairy cell leukemia by sensitive detection of the BRAF-V600E mutation

B-Raf Regulation of Integrin α4β1-mediated Resistance to Shear Stress through Changes in Cell Spreading and Cytoskeletal Association in T Cells

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