Dataset Information

How I treat hairy cell leukemia.

ABSTRACT: The description of hairy cell leukemia as a specific clinical entity was published 50 years ago. The clinical outcome for patients was hampered by ineffective chemotherapy, and splenectomy was the major therapeutic approach to improve peripheral blood counts. The median survival after diagnosis was 4 years. With the introduction of alpha-interferon in 1984, marked improvements in patient responses were observed. Shortly thereafter, the introduction of the purine nucleoside analogs transformed this disease into a highly treatable form of leukemia, and patients with the classic form of this rare leukemia now have a near-normal life expectancy. However, other clinical entities mimicking this disease do not respond; thus, accurate diagnosis is important. Immunophenotypic features in classic hairy cell leukemia show that the leukemic cells express CD11c, CD25, CD103, and CD123 and display bright CD20. Despite the high percentage of durable complete remissions with modern therapy, the long-term disease-free survival curves have not reached a plateau. Many patients who achieve a complete remission by morphologic criteria have minimal residual disease demonstrable by either flow cytometry or immunohistochemical staining, and this population may be at higher risk for earlier relapse. Continued clinical research is essential to optimize therapy for this disease.

SUBMITTER: Grever MR

PROVIDER: S-EPMC2803689 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

How I treat hairy cell leukemia.

Grever Michael R MR

Blood 20091020 1

The description of hairy cell leukemia as a specific clinical entity was published 50 years ago. The clinical outcome for patients was hampered by ineffective chemotherapy, and splenectomy was the major therapeutic approach to improve peripheral blood counts. The median survival after diagnosis was 4 years. With the introduction of alpha-interferon in 1984, marked improvements in patient responses were observed. Shortly thereafter, the introduction of the purine nucleoside analogs transformed th ...[more]

PMID: 19843881

Similar Datasets

Project description: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).

Project description:Background: Hairy cell leukemia (HCL) is a rare chronic B-cell lymphoproliferative disorder. It has two pathological subtypes: classical HCL (HCL-C) and HCL-variant (HCL-V). HCL-C and HCL-V are distinct in morphology and immunophenotype. Their differentiation is important for patient management and clinical outcome, with HCL-V responding poorly to conventional HCL treatments. Recently, whole genomic sequencing has been used to identify the difference between HCL-C and HCL-V and mutation of BRAFV600E has been proved to be a molecular hallmark of HCL-C. However, BRAF inhibitors were not effective in all HCL-C cases and HCL-V seems be lack of the high-frequency mutations. Therefore, it is necessary to compare the genomic changes between HCL-C and HCL-V by high-resolution studies, especially in Chinese population, the genomic alterations of HCL have rarely be reported. Methods: In this study, the clinical features of a total of 18 Chinese HCL patients were described. Single nucleotide polymorphism (SNP) array analysis was performed to evaluate the genomic copy number alterations (CNA) and copy neutral loss of heterozygosity (CN-LOH) on six HCL-Vs with CD25-/BRAFV600E- and four HCL-Cs with CD25+/BRAFV600E+. Results: A total of 24 CNAs including seven chromosomal gains and 17 chromosomal losses, and 22 CN-LOHs were revealed. Five of the six cases of HCL-V showed 15 CNAs including four cryptic chromosomal gains and 11 chromosomal losses. Overlapping regions involving micro-deletion of chromosome 2q13 and large chromosomal loss of 14q were showed in HCL-V. In HCL-C, a total of nine CNAs were revealed in three of the four cases including three chromosomal gains and six chromosomal losses. No overlapping area was observed among the CNVs. 15 CN-LOHs were showed in five of the six cases of HCL-V and seven CN-LOHs was demonstrated in all of the four HCL-Cs. Conclusions: Comparing to Westerners, a relatively higher proportion of HCL-V in all HCL is observed in this study. CNAs and CN-LOHs were common in both HCL-V and HCL-C but the CNAs were different in them. HCL-C was characterized with the higher ratio of large chromosomal changes but lacked of recurrent CNAs, while HCL-V was presented with the higher incidence of cryptic CNAs and recurrent CNAs involving tumor-associated genes. It is necessary to further investigate the association of the genes, such as NPHP1 and TRAF3 genes, and HCL-V in the future study.

Dataset Information

How I treat hairy cell leukemia.

Publications

How I treat hairy cell leukemia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure