Key differentiating features of classical and variant HCL are listed briefly in Table 2. A number of recent studies have contributed additional potential markers of inferior response to therapy and worse overall prognosis [21], [24], [25] and [26]. Studies have suggested that

patients with hairy cell leukemia expressing an un-mutated immunoglobulin gene may resemble un-mutated CLL in terms of worse prognosis and shortened survival. Similarly, TP53 defects have been linked with decreased progression-free survival after initial therapy with a purine analog. Recently, Kreitman and colleagues found that patients with hairy cell leukemia expressing IGHV4-34 also have an inferior therapeutic response, indicating that this may be of importance in the risk stratification Alpelisib manufacturer analysis at the time of diagnosis. In fact, although this subset of patients’ leukemias may resemble classic hairy cell leukemia immunophenotypically, BRAF V600E mutation is usually absent, as it is in variant HCL [21]. Additional investigation by whole-genome sequencing has further linked BRAFwt, selleck IGHV4-34+

classical HCL pathogenically to variant HCL through the discovery of a high percentage of MAP2K1 mutations, suggesting a critical role for the RAF–MEK–ERK signaling pathway in both classical and variant HCL [26]. In many ways, the patients with these differing features represent unique subsets of HCL and constitute molecular variants of the disease. While the immunophenotypic profile of the leukemic cells has been most often utilized to establish

the basic diagnosis, molecular Ribonucleotide reductase profiling may have a role in the identification of patients who are more likely to achieve durable remissions to standard therapy. Consequently, if validated, the use of these refined predictors of response and molecular classifications may not only justify therapy with novel approaches, but will also guide, which targeted therapy may be most appropriate. Infectious complications have been a hallmark of the clinical course of patients with hairy cell leukemia, and were the most frequent cause of death before effective therapy [5] and [27]. Patients may be significantly immunocompromised as a result of the underlying disease or following immunosuppressive chemotherapy. The propensity to bacterial and atypical opportunistic infections has been attributed to the granulocytopenia and absolute monocytopenia observed in the classic form of the disease, with disrupted mononuclear cell and lymphocyte function additionally underlying an immunocompromised state [28], [29] and [30]. Atypical infections with mycobacterial organisms reflect difficulties in handling intracellular pathogens, while prolonged neutropenia may lead to an increased risk of invasive fungal infections [31].