Evaluation of BRAFV600E, NRAS and KRAS Mutations As Well As IGHV Usage for Diagnostic Use in Hairy Cell Leukemia, Hairy Cell Leukemia-Variant and Splenic Marginal Zone Lymphoma.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2679-2679
Author(s):  
Susanne Schnittger ◽  
Frank Dicker ◽  
Christiane Eder ◽  
Sabine Jeromin ◽  
Tamara Alpermann ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Hairy Cell Leukemia ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Leukemic Cells ◽  
Multiparameter Flow Cytometry ◽  
Splenic Marginal Zone Lymphoma ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Equity Ownership

Abstract Abstract 2679 Background: The BRAF V600E mutation has recently been discovered in nearly all cases of hairy cell leukemia (HCL), but not in cases of HCL-variant (HCL-v). However, this perfect correlation has been challenged by studies reporting HCL cases without BRAF V600E. Interestingly, the immunoglobulin heavy chain variable region gene IGHV4–34, which has been associated with poor prognosis in HCL, appeared exclusively and to a high percentage in these BRAF V600E-negative cases of classic HCL and also in HCL-v (Xi et al., Blood, 2011). Further, splenic marginal zone lymphoma (SMZL) is a disease closely related to HCL and HCL-v and BRAF has been shown to be unmutated in this entity. Aims: 1. To characterize our cohorts of HCL, HCL-v and SMZL for the presence of BRAF V600E and to correlate the results with IGHV gene usage. 2. We hypothesized that other genes of the RAF/RAS pathway might be affected. Thus we analysed NRAS, and KRAS in addition to BRAF for mutations in all three entities. Methods: We analyzed the bone marrow or peripheral blood of 314 cases (182 cases with HCL, 49 cases with HCL-v, and 83 cases with SMZL) at diagnosis as confirmed by multiparameter flow cytometry and cytomorphology. The BRAF V600E mutation was analyzed by an mRNA-based reverse transcription allele-specific real-time quantification (RQ-PCR) assay. The BRAF V600E expression was calculated as %BRAF V600E/BRAF wt. NRAS and KRAS were analyzed by melting curve analysis and subsequent Sanger sequencing. IGHV genes and mutation status were analyzed by the use of Biomed-2 primers. An identity of ≥98% of the analyzed IGHV sequence compared to published germline sequences was considered an unmutated IGHV status. Results: In our cohort the median percent leukemic cells was 16% (range 0.2–74%) for HCL, 33% (range 5–59%) for HCL-v and 29% (range: 1–84%) for SMZL as determined by multiparameter flow cytometry. The BRAF V600E mutation was detected in 178/182 (97.8%) of HCL cases, whereas 0/49 of HCL-v and 0/83 SMZL were positive. Thus, the BRAF V600E mutation is 100% specific for HCL regarding these three entities. The median BRAF V600E expression ratio of positive cases was 14.2 (range 0.22 – 280.3). After normalization to % pathological cells as assessed by multiparameter flow cytometry the median ratio was 173 (range:22–1,788). However, in 4 cases with 4%, 8%, 28% and 66% percent leukemic cells by multiparameter flow cytometry, which is within the clone size that can be clearly detected by the BRAF V600E-specific RQ-PCR assay, no mutation was detected. Thus, BRAF V600E detection used for the identification of HCL has a sensitivity of 97.8%. Further, NRAS and KRAS mutation screening in all cases with HCL, HCL-v, and SMZL did not detect any mutation except for one case with SMZL that harboured an NRAS Gly12Asp mutation. This case was found to have an MDS in parallel and thus the mutation more likely belongs to the MDS clone. Thus, analysis of NRAS and KRAS mutations does not further improve diagnostics in these diseases. Further, we analyzed the IGHV usage in all 4 BRAF unmutated HCL and in additional 60 cases (total n=64) with HCL and 41 cases with HCL-v. IGHV4–34 usage was very frequent in HCL-v with 14/41 (34.1%). In contrast, it was never detected in HCL including the BRAF wildtype cases. Thus, we were not able to confirm the usage of the IGHV4–34 gene, which was previously suggested for BRAF V600E negative HCL. On the other hand IGHV5–51 was most frequently found in HCL (9/64, 14.1%) but never detected in HCL-v. We detected an unmutated IGHV status in 12/62 (19.4%) of HCL, which was less frequent compared to 14/40 (35.0%) in HCL-v (p = 0.095). The IGHV mutation status was unmutated in 9/11 (81.8%) IGHV4–34 cases (100% identity to germline each). The four cases of HCL, which lacked BRAF V600E mutation, expressed the IGHV genes IGHV1–3*01 (96.5% identity), IGHV1–69*02 (94.0% identity), IGHV3–9*01 (96.9% identity) and IGHV6-1*01 (99.0% identity), which were also expressed by various BRAF V600E positive HCL cases in our cohort. Conclusions: 1) In our cohort of 314 cases with HCL, HCL-v, and SMZL we confirm a high specificity (100%) and sensitivity (97.8%) for BRAF V600E mutations to detect HCL. 2) Other RAS pathway mutations (NRAS, KRAS) were not detected in any of the three analysed entities. 3) In the 4 rare cases of HCL with BRAF wt we were not able to confirm the previously postulated IGHV4–34 usage. 4) IGHV4–34 further delineates classic HCL from HCL-v. Disclosures: Schnittger: MLL Munich Leukemia Laboratory: Equity Ownership. Dicker:MLL Munich Leukemia Laboratory: Employment. Eder:MLL Munich Leukemia Laboratory: Employment. Jeromin:MLL Munich Leukemia Laboratory: Employment. Alpermann:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Equity Ownership.

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

Blood ◽  
2012 ◽  
Vol 119 (1) ◽  
pp. 192-195 ◽  
Author(s):  
Enrico Tiacci ◽  
Gianluca Schiavoni ◽  
Francesco Forconi ◽  
Alessia Santi ◽  
Livio Trentin ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Genetic Diagnosis ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Leukemic Cells ◽  
Splenic Marginal Zone Lymphoma ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Genetic Event ◽  
Specific Pcr

Abstract 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. This approach detected BRAF-V600E in all 123 leukemic HCL samples investigated containing as few as 0.1% leukemic cells. BRAF-V600E was detected at different time points during the disease course, even after therapy, pointing to its pivotal role in HCL pathogenesis and maintenance of the leukemic clone. Conversely, 115 non-HCL chronic B-cell neoplasms, including 79 HCL-like disorders, were invariably negative for BRAF-V600E. This molecular assay is a powerful tool for improving the diagnostic accuracy in HCL.

scholarly journals Genomics of Hairy Cell Leukemia

2017 ◽  
Vol 35 (9) ◽  
pp. 1002-1010 ◽  
Author(s):  
Enrico Tiacci ◽  
Valentina Pettirossi ◽  
Gianluca Schiavoni ◽  
Brunangelo Falini
Keyword(s):  
B Cell ◽  
Hairy Cell Leukemia ◽  
Ex Vivo ◽  
Braf Inhibitor ◽  
Braf V600e ◽  
Leukemic Cells ◽  
Splenic Marginal Zone Lymphoma ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Purine Analogs

Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with unique clinicopathologic features and an initial exquisite sensitivity to chemotherapy with purine analogs; however, the disease relapses, often repeatedly. The enigmatic pathogenesis of HCL was recently clarified by the discovery of its underlying genetic cause, the BRAF-V600E kinase-activating mutation, which is somatically and clonally present in almost all patients through the entire disease spectrum and clinical course. By aberrantly activating the RAF-MEK-ERK signaling pathway, BRAF-V600E shapes key biologic features of HCL, including its specific expression signature, hairy morphology, and antiapoptotic behavior. Accompanying mutations of the KLF2 transcription factor or the CDKN1B/p27 cell cycle inhibitor are recurrent in 16% of patients with HCL and likely cooperate with BRAF-V600E in HCL pathogenesis. Conversely, BRAF-V600E is absent in other B-cell neoplasms, including mimickers of HCL that require different treatments (eg, HCL-variant and splenic marginal zone lymphoma). Thus, testing for BRAF-V600E allows for a genetics-based differential diagnosis between HCL and HCL-like tumors, even noninvasively in routine blood samples. BRAF-V600E also represents a new therapeutic target. Patients’ leukemic cells exposed ex vivo to BRAF inhibitors are spoiled of their HCL identity and then undergo apoptosis. In clinical trials of patients with HCL who have experienced multiple relapses after purine analogs or who are refractory to purine analogs, a short course of the oral BRAF inhibitor vemurafenib produced an almost 100% response rate, including complete remission rates of 35% to 42%, without myelotoxicity. To further improve on these results, it will be important to clarify the mechanisms of incomplete leukemic cell eradication by vemurafenib and to explore chemotherapy-free combinations of a BRAF inhibitor with other targeted agents (eg, a MEK inhibitor and/or an anti-CD20 monoclonal antibody).

Resolution of Hairy Cell Leukemia Minimal Residual Disease by Both BRAF and Clone-Specific Real-Time Quantitative PCR (RQ-PCR) After Treatment with Moxetumomab Pasudotox.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2896-2896 ◽  
Author(s):  
Robert J. Kreitman ◽  
Evgeny Arons ◽  
Sapolsky Jeffrey ◽  
Laura Roth ◽  
Hong Zhou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Hairy Cell Leukemia ◽  
Residual Disease ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Specific Primer ◽  
Minimal Residual

Abstract Abstract 2896 Background: Moxetumomab pasudotox is an anti-CD22 recombinant immunotoxin containing truncated Pseudomonas exotoxin which was recently reported to achieve a complete remission rate of 46% in 28 patients with relapsed/refractory hairy cell leukemia (HCL). An additional 20 patients were treated at the highest dose level and are now fully evaluable for response and minimal residual disease (MRD) determinations. RQ-PCR using clone-specific primers and a clone-specific TaqMan probe is capable of detecting one HCL cell in 106normal cells. Recently reported methods to detect the HCL-associated BRAF V600E mutation include pyrosequencing (5–10% sensitivity) and PCR (0.1–0.23% sensitivity). Methods: Moxetumomab pasudotox was administered to 16 patients at 5–40 ug/Kg every other day for 3 doses (QODx3) and to 32 patients at 50 ug/Kg QODx3, via 1–16 (median 4) cycles per patient at 4-week intervals. Complete remission (CR) required resolution of cytopenias and elimination of HCL in the blood and marrow by standard microscopy, but MRD could be present by flow cytometry of blood or bone marrow aspirate (BMA) or immunohistochemistry (IHC) of the bone marrow biopsy (BMBx). Blood and marrow from patients were also tested by PCR using consensus primers. When immunoglobulin (Ig) rearrangements could be cloned, RQ-PCR using clone-specific primer and probe was performed. To detect MRD by the BRAF V600E mutation, BRAF quantitative PCR (BRAF-qPCR) was performed on cDNA samples, using mutant-specific primer, and SYBR-Green detection followed by melting point analysis. MRD testing for BRAF-qPCR, unlike clone-specific RQ-PCR, did not require prior cloning of the Ig rearrangement. Results: All 198 cycles of moxetumomab administered to 48 patients were evaluable for toxicity and response. No dose limiting toxicity was observed, although 2 patients as previously reported had a grade 2 hemolytic uremic syndrome with transient grade 1 platelet and creatinine abnormalities. Of the 48 HCL patients at all dose levels, there were 26 (54%) CRs, with an overall response rate (ORR) of 88%. Of 32 at 50 ug/Kg QODx3, there were 19 (59%) CRs with an ORR of 91%. Of these 19 CRs, 11 (58%) achieved MRD negativity by repeated flow cytometry of both BMA and blood and IHC of BMBx. Flow cytometry of the BMA was the most sensitive conventional test of MRD. Of the 9 CRs at 50 ug/Kg QODx3 evaluable by clone-specific RQ-PCR of blood, 5 negative were also flow-negative, and 4 positive were also flow-positive (p=0.008). BRAF-qPCR on cDNA from limiting dilutions of BRAF V600E+ Colo-205 cells into BRAF wild-type cells achieved consistent detection at 1:105dilution (0.001%). Of 10 flow-negative CRs at 50 ug/Kg QODx3 evaluated by BRAF-qPCR, all 10 (100%) were BRAF-qPCR negative, including 4 which were nonevaluable by RQ-PCR due to inability to clone the Ig rearrangements prior to treatment. Currently 12 (63%) of the 19 CRs at 50 ug/Kg QODx3 are ongoing at 6–47 (median 21) months, including 10 (91%) of 11 MRD-negative vs 2 (25%) of 8 MRD+ CRs (p=0.006). Conclusions: Moxetumomab pasudotox is active in relapsed and refractory HCL and has a safety profile supporting further development for this disease. Retreatment on this trial could not necessarily be extended to achieve MRD-negative BMAs or molecular remission by RQ-PCR using sequence-specific or BRAF primers. However, these tests might be useful in the future to guide retreatment, optimize CR durability and possibly eradicate the HCL clone in selected patients. This summary contains investigator reported data. This study was sponsored by MedImmune, LLC, and supported by NCI's Intramural Research Program and the Hairy Cell Leukemia Research Foundation. Disclosures: Kreitman: NIH: Co-inventor on the NIH patent for Moxetumomab Pasudotox, Co-inventor on the NIH patent for Moxetumomab Pasudotox Patents & Royalties. Off Label Use: Moxetumomab Pasudotox is an experimental agent for CD22+ hematologic malignancies. FitzGerald:NIH: Coinventor on the NIH patent for Moxetumomab Pasudotox, Coinventor on the NIH patent for Moxetumomab Pasudotox Patents & Royalties. Fei:AstraZeneca: Stock, Stock Other; MedImmune, LLC: Employment. Ibrahim:AstraZeneca: Stocks, Stocks Other; MedImmune: Employment. Pastan:NIH: Coinventor on NIH patent for moxetumomab pasudotox, Coinventor on NIH patent for moxetumomab pasudotox Patents & Royalties.

Development and Validation of a Real Time Quantification Assay to Detect and Monitor BRAFV600E-Mutations in Hairy Cell Leukemia,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3674-3674
Author(s):  
Susanne Schnittger ◽  
Torsten Haferlach ◽  
Nicole Wendland ◽  
Madlen Ulke ◽  
Vera Grossmann ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Employment Equity ◽  
Log Reduction ◽  
Equity Ownership ◽  
Normal Controls

Abstract Abstract 3674 Introduction: So far, the diagnosis of hairy cell leukemia (HCL) was based on cytomorphology, immunophenotyping and histology. Monitoring of the disease during therapy is most sensitively performed by immunophenotyping. The genetics underlying HCL was unclear until very recently, when a BRAF V600E mutation was described to occur in all patients (48/48) with HCL (Tiacci et al., NEJM: 364, 2305–15, 2011). Aim: The aim of this study was to establish and evaluate a reliable genetic test to detect and monitor BRAFV 600E mutations with high specificity and sensitivity. Methods: After testing different variants of DNA or RNA based direct sequencing and melting curve assays we decided for an mRNA-based reverse transcription real time quantification (RQ-PCR) assay that yielded the best sensitivity and specificity. This assay includes a BRAF V600E mutation-specific primer and an additional mismatch nucleotide that further enhances the specific detection of mutated transcripts. The mutated transcripts were normalized against BRAF wildtype (BRAF wt) transcripts. Values are given in %BRAF V600E/BRAF wt. In total, 259 samples were analysed with this assay. First, the specificity of the assay was analysed in 96 samples with a “non-HCL” diagnosis (AML n=9, MDS n=7, MPN n=13, CML n=4, CML in MMR n=10, CMML n=4, CEL n=2, T-ALL n=1, B-ALL n=2, B-NHL n=35, CLL n=2, non-malignant diseases n=7). These samples were used to establish the non-specific background of the assay that can be caused by the normal wild type allele. Subsequently, 124 patients with a proven diagnosis of HCL were analysed (31 females/93 males median age: 59.6 yrs, range 24.3–88.4 yrs). In addition, 16 patients with HCL-variant were analyzed. In 19 of the HCL cases additional follow-up samples were investigated (range, 1–4 samples per patient, total number n=25). Results: Limited dilution series of DNA of 2 cases with highly infiltrated HCL in DNA of a normal control revealed a sensitivity of this assay of 1/10e4-1/10e5. Unspecific %BRAF V600E/BRAF wt values of “non-HCL” controls were very low (median: 0.003, range: 0.000–0.030, SD: 0.005). In the 16 cases with HCL-variant the %BRAF V600E/BRAF wt values were in the same range as in the “non-HCL” controls (median: 0.006, range: 0.000–0.012, SD: 0.004). Based on these results the cut-off level was defined as 0.018 %BRAF V600E/BRAF wt (3xSD over the median). 117/124 cases with proven HCL (94.4%) had a %BRAF V600E/BRAF wt expression that was above the cut-off as defined by normal controls (median: 16.9, range 0.077–280.3). There was a highly significant correlation between the BRAF expression and the percentage of HCL cells as determined by immunophenotyping (r=0.741, p=0.001). The remaining 7/124 (5.6%) HCL patients had %BRAF V600E/BRAF wt values in the range of normal controls and thus are regarded as not carrying the typical BRAF V600E. Deep sequencing using the 454 technology did not reveal any rare BRAF mutations even not at a low levels in any of these 7 cases (median coverage: 427 reads, range: 199–823 reads). In the 19 BRAF V600E-positive patients with follow-up samples an up to 4 log reduction of the %BRAF V600E/BRAF wt was observed during therapy. Comparison of this log reduction with the log reduction as determined by immunophenotyping again revealed a close correlation (r=0.892, p<0.001). In 5 samples values in remission were in the range of negative controls. In one case a relapse was predictable one month before cytomorphologic relapse appeared by an increasing %BRAF V600E/BRAF wt level, paralleling with an increasing percentage of HCL cell as determined by immunophenotyping. Conclusion: 1) BRAF V600E is a new marker that is useful for diagnosis of HCL. 2) This new assay can detect HCL in >94% of cases and BRAF V600E mutations with a specificity of 100%. 3) Given the high sensitivity of 1/10e4-1/10e5 it serves a valuable tool for minimal residual disease detection in HCL. Disclosures: Schnittger: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Wendland:MLL Munich Leukemia Laboratory: Employment. Ulke:MLL Munich Leukemia Laboratory: Employment. Grossmann:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.

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

Blood ◽  
2012 ◽  
Vol 119 (1) ◽  
pp. 188-191 ◽  
Author(s):  
Luca Arcaini ◽  
Silvia Zibellini ◽  
Emanuela Boveri ◽  
Roberta Riboni ◽  
Sara Rattotti ◽  
...  
Keyword(s):  
Molecular Marker ◽  
B Cell ◽  
Hairy Cell Leukemia ◽  
Lymphoproliferative Disorders ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Splenic Marginal Zone Lymphoma ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Specific Pcr

Abstract 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.

Identification of the BRAF V600E mutation in Japanese patients with hairy cell leukemia and related diseases using a quenching probe method

2018 ◽  
Vol 108 (4) ◽  
pp. 416-422
Author(s):  
Hidekazu Itamura ◽  
Masaru Ide ◽  
Akemi Sato ◽  
Naoko Sueoka-Aragane ◽  
Eisaburo Sueoka ◽  
...  
Keyword(s):  
Hairy Cell Leukemia ◽  
Japanese Patients ◽  
Braf V600e Mutation ◽  
Probe Method ◽  
Braf V600e ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Quenching Probe

scholarly journals Usefulness of Dual Immunohistochemistry Staining in Detection of Hairy Cell Leukemia in Bone Marrow

2019 ◽  
Vol 153 (3) ◽  
pp. 322-327 ◽  
Author(s):  
Gaurav K Gupta ◽  
Xiaoping Sun ◽  
Constance M Yuan ◽  
Maryalice Stetler-Stevenson ◽  
Robert J Kreitman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Hairy Cell Leukemia ◽  
Predictive Value ◽  
Lymphoid Cells ◽  
Multiparameter Flow Cytometry ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Flow Cytometry Data ◽  
Flow Cytometric Data

Abstract Objectives We evaluated efficacy of two dual immunohistochemistry (IHC) staining assays in assessing hairy cell leukemia (HCL) involvement in core biopsies and compared the results with concurrently collected flow cytometric data. Methods Overall, 148 patients with HCL (123 male, 25 female; mean age: 59.8 years; range: 25-81 years) had multiparameter flow cytometry performed using CD19, CD20, CD22, CD11c, CD25, CD103, CD123, surface light chains, CD5, and CD23. In parallel, bone marrow IHC was done using PAX5/CD103 and PAX5/tartrate-resistant alkaline phosphatase (TRAP) dual IHC stains. Results Overall sensitivity of dual IHC stains was 81.4%, positive predictive value was 100%, and negative predictive value was 81.7%. All IHC-positive cases concurred with flow cytometry data, even when HCL burden was extremely low in the flow cytometry specimens (as low as 0.02% of all lymphoid cells). Conclusions Dual IHC stain is a sensitive tool in detecting HCL, even in cases with minimal disease involvement.

scholarly journals Hairy cell leukemia with CCND1/IGH fusion gene and BRAF V600E mutation

2020 ◽  
Vol 13 ◽  
pp. 100197 ◽  
Author(s):  
Zaid Abdel Rahman ◽  
Firas Muwalla ◽  
Liuyan Jiang ◽  
James Foran
Keyword(s):  
Hairy Cell Leukemia ◽  
Fusion Gene ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Hairy Cell ◽  
Cell Leukemia

scholarly journals Both variant and IGHV4-34–expressing hairy cell leukemia lack the BRAF V600E mutation

Blood ◽  
2012 ◽  
Vol 119 (14) ◽  
pp. 3330-3332 ◽  
Author(s):  
Liqiang Xi ◽  
Evgeny Arons ◽  
Winnifred Navarro ◽  
Katherine R. Calvo ◽  
Maryalice Stetler-Stevenson ◽  
...  
Keyword(s):  
B Cell ◽  
Hairy Cell Leukemia ◽  
Poor Prognosis ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Wild Type ◽  
Ighv Gene ◽  
Gene Usage

Abstract Recently, the BRAF V600E mutation was reported in all cases of hairy cell leukemia (HCL) but not in other peripheral B-cell neoplasms. We wished to confirm these results and assess BRAF status in well-characterized cases of HCL associated with poor prognosis, including the immunophenotypically defined HCL variant (HCLv) and HCL expressing the IGHV4-34 immunoglobulin rearrangement. Fifty-three classic HCL (HCLc) and 16 HCLv cases were analyzed for BRAF, including 5 HCLc and 8 HCLv expressing IGHV4-34. BRAF was mutated in 42 (79%) HCLc, but wild-type in 11 (21%) HCLc and 16 (100%) HCLv. All 13 IGHV4-34+ HCLs were wild-type. IGHV gene usage in the 11 HCLc BRAF wild-type cases included 5 IGHV4-34, 5 other, and 1 unknown. Our results suggest that HCLv and IGHV4-34+ HCLs have a different pathogenesis than HCLc and that a significant minority of other HCLc are also wild-type for BRAF V600.

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