Evidence of canonical somatic hypermutation in hairy cell leukemia

Arons, Evgeny; Roth, Laura; Sapolsky, Jeffrey; Suntum, Tara; Stetler‐Stevenson, Maryalice; Kreitman, Robert J.

doi:10.1182/blood-2010-11-316737

Cited by 33 publications

(32 citation statements)

References 45 publications

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“…1 Sixty-three of the 69 cases were molecularly characterized with respect to IGHV gene usage, and most were previously reported. 18 Thirteen (21%) of 63 expressed IGHV4-34, including 5 HCLc, and 8 HCLv ( Table 1).…”

Section: Resultsmentioning

confidence: 99%

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

Xi¹,

Arons

Navarro³

et al. 2012

Blood

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Section: Resultsmentioning

confidence: 99%

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

Xi¹,

Arons

Navarro³

et al. 2012

Blood

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“…Several recent studies have better characterized the cell of origin and molecular events occurring in HCL and modern techniques have allowed a better characterization of disease biology. 30,31 Here, we have demonstrated the feasibility and potential benefit from chemo-immunotherapy in these patients. Longer follow-up of our patients is needed to clearly determine the superiority of the combination over cladribine alone.…”

Section: Discussionmentioning

confidence: 99%

Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia

Ravandi¹,

O’Brien²,

Jorgensen

et al. 2011

Blood

107

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We conducted this study to determine the feasibility and safety of cladribine followed by rituximab in patients with hairy cell leukemia including the variant form (HCLv). Cladribine 5.6 mg/m 2 given IV over 2 hours daily for 5 days was followed ϳ 1 month later with rituximab 375 mg/m 2 IV weekly for 8 weeks.Responses were recorded and BM minimal residual disease (MRD) was evaluated after the completion of rituximab. Thirty-six patients have been treated in- IntroductionOver the past quarter century, we have witnessed remarkable progress in the treatment of patients with hairy cell leukemia (HCL). 1,2 The nucleoside analogs cladribine and pentostatin have made a significant impact in the treatment of HCL producing complete response (CR) rates of 80% to 90%. 3,4 Long-term follow-up of patients treated with these agents have shown that about one-fourth to one-third of patients relapse after a follow-up of 3 to 4 years with little difference between the 2 drugs, in terms of durability of response. [5][6][7] Previous reports have suggested that the quality of the initial response can be predictive of the outcome, with a longer disease-free survival in those achieving a CR after initial therapy as opposed to those with lesser responses. [7][8][9] This has led to the suggestion by some authors to persist with therapy, in the absence of toxicity, until a CR is attained, 7 and to efforts to eradicate minimal residual disease (MRD) after the initial therapy. This is particularly important as the median age of patients with HCL is in the 50s, and subsequent CRs may be shorter in duration with successive therapy. 5,10,11 Determination of the risk of relapse based on the persistence of MRD determined by immunohistochemistry (IHC) using anti-CD45RO, anti-CD20, and DBA.44 in paraffin-embedded BM sections was first reported by the group from Northwestern University. 12 More recently, more precise methods using immunophenotyping by flow cytometry, and consensus primer or clonespecific PCR analysis of Ig receptors, have been used to detect MRD in patients with HCL. [13][14][15] Whether eradication of MRD should be a goal of therapy in the initial management of patients with HCL remains a subject of discussion. 16 Sigal et al have reported that among 19 patients with HCL in continuous CR after 1 course of cladribine (median time from therapy, 16 years, [range, 11-21 years]) in whom BM samples were available, 7 (37%) had MRD, and 3 (16%) had morphologic evidence of HCL suggesting that patients with MRD or even morphologic disease can live many years without a hematologic relapse. 17 We have previously reported on the efficacy of rituximab in eradicating MRD in patients with HCL treated with cladribine. 14 Among the 13 patients, reported MRD assessed by consensus primer PCR or flow cytometry was eradicated in 92% at 3 months. We have reported a brief summary of this phase 2 trial including patients with relapsed disease recently for a collective report of a meeting of hairy cell leukemia experts at the National Institutes of Heal...

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“…4,5 Most HCL cases (80%-90%) are characterized by somatic hypermutation in the IGHV gene. 6,7 The frequency of unmutated IGHV is much lower in classic HCL than in HCLvariant (HCLv) (17% vs 54%; P<.001). 7 Unmutated IGHV may serve as a prognostic factor for poorer outcomes with conventional therapies because it has been associated with primary refractoriness to purine analogue monotherapy and a more rapid disease progression.…”

Section: Diagnosismentioning

confidence: 99%

“…6,7 The frequency of unmutated IGHV is much lower in classic HCL than in HCLvariant (HCLv) (17% vs 54%; P<.001). 7 Unmutated IGHV may serve as a prognostic factor for poorer outcomes with conventional therapies because it has been associated with primary refractoriness to purine analogue monotherapy and a more rapid disease progression. 8 The BRAF V600E mutation has been reported in most patients with classic HCL but not in those with other B-cell leukemias or lymphomas.…”

Section: Diagnosismentioning

confidence: 99%

Hairy Cell Leukemia, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology

Wierda

Byrd

Abramson

et al. 2017

J Natl Compr Canc Netw

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Evidence of canonical somatic hypermutation in hairy cell leukemia

Cited by 33 publications

References 45 publications

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

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

Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia

Hairy Cell Leukemia, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology

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