Note: All samples should be forwarded to LabPlus at room temperature within 24hours.
Note: Peripheral blasts in Hairy cell Leukaemia are often rare. Even after B cell enrichment, peripheral blood may not yield sufficient blasts for successful analysis. Wherever possible Bone Marrow aspirate should be used as the preferred specimen.
While the BRAF gene has been reported as the most commonly mutated kinase in human cancer, its interest to the field of haematology lies in its use as a diagnostic tool for classic Hairy-cell leukaemia (HCLc) (Tiacci et al., 2011) . In 2011 Tiacci et al. discovered the BRAF mutation p.Val600Glu in all HCLc samples tested (48), but not in any other B-cell lymphomas or leukaemias (195) analysed. The additional B-cell malignancies tested in the Tiacci et al. study included some that have clinical and histological similarities to HCLc, including variant Hairy-cell leukaemia (HCLv) which has a histologically similar presentation to HCLc but different treatment and prognosis. This finding offers the opportunity to improve the differential diagnosis of HCLc and HCLv by analysis of BRAF for the p.Val600Glu mutation. The work of Tiacci et al. has been verified in further studies and there is general agreement that detection of BRAF p.Val600Glu mutations along with clinical and morphological signs is diagnostic of HCLc (Arcaini et al., 2012) .
HCLc is characterised by the presence of splenomegaly, progressive pancytopenia, rare circulating blasts, absence of lymphadenopathy and the presence of leukaemic B-cell infiltration of the bone marrow, liver and spleen. The blast cells themselves have particularly characteristic "hairy" looking projections (Sharpe & Bethel, 2006) . Progression of HCLc is typically indolent and treatment is generally successful. However, treatment with purine nucleoside analogues can be associated with adverse events and some patients remain refractory (Tiacci et al., 2011) . The discovery of BRAF p.Val600Glu mutations in HCLc opens the possibility of the use of specific inhibitors of activated BRAF for treatment in HCLc (Sharma et al., 2012) .
References:
Arcaini, L., Zibellini, S., Boveri, E., Riboni, R., Rattotti, S., Varettoni, M. (2012). The BRAF V600E mutation in hairy cell leukemia and other mature B-cell neoplasms. Blood, 119(1), 188-191.
Sharma, A., Shah, S. R., Illum, H., Dowell, J., Sharma, A., Shah, S. R. (2012). Vemurafenib: targeted inhibition of mutated BRAF for treatment of advanced melanoma and its potential in other malignancies. Drugs, 72 (17), 2207-2222.
Sharpe, R. W., & Bethel, K. J. (2006). Hairy cell leukemia: diagnostic pathology. Hematology - Oncology Clinics of North America, 20(5), 1023-1049.
Tiacci, E., Trifonov, V., Schiavoni, G., Holmes, A., Kern, W., Martelli, M. P. (2011). BRAF mutations in hairy-cell leukemia. N Engl J Med, 364(24), 2305-2315.
To contact the Molecular Haematology team please call:
| Auckland City Hospital | (09) 307 4949 |
| Lablink | ext 22000 |
| Prof. Peter Browett (Haematologist) | ext 9090-86281 |
| Dr. Imogen Caldwell (Haematologist) | ext 22006 |
| Nikhil Ghallayan (Section Leader) | ext 22005 |
| Molecular Haematology Office | ext 22005 |
For more information about the Molecular Haematology service at LabPLUS: