Hairy cell leukaemia: biological and clinical overview from immunogenetic insights

Abstract

Hairy cell Leukaemia (HCL) is a rare neoplasm of peripheral B cells which represents a paradox in oncology. Despite its largely unknown origin and behaviour, HCL is one of the few example of dramatic success in the treatment of a malignancy. The recent steps forward to understanding the biology of HCL from immunogenetic and genomic studies have recently provided new insight into diagnosis and prognosis. Several data from immunoglobulin gene (IG) analysis have provided hints regarding the cell of origin and the ongoing selective interactions of the tumour BCR with environmental stimuli. It has also recently emerged that an unmutated status of the HCL IG can be associated with failure to respond to cladribine, genetic abnormalities indicative of poor outcome and aggressive disease. These observations suggest a central role of the tumour B-cell receptor in defining the outcome of HCL and that that IG gene analysis may have biological and prognostic relevance. Hopefully, IG analysis will help tailor treatment strategies for the most aggressive cases.

Massive splenomegaly

“…Most authors define massive splenomegaly when the spleen reaches the iliac crest, crosses the midline or weights more than 1500 g. The most common aetiologies of massive splenomegaly include haematological disorders (chronic myeloid leukamia, agnogenic myeloid metaplasia, polycythaemia vera, essential thrombocythaemia, indolent lymphomas, hairy cell leukaemia, β-thalassaemia major), infectious diseases (visceral leishmaniasis, malaria) and infiltrative conditions (Gaucher disease) 1 2…”

B Cell Lymphomas

“…HCL is an indolent lymphoma involving bone marrow and splenic red pulp. Hepatomegaly is observed in nearly half of patients, and lymph nodes are rarely enlarged [7]. Until 1984, splenectomy was considered the treatment of choice, associated with good therapeutic response.…”

The microenvironment in hairy cell leukemia: pathways and potential therapeutic targets

“…Chronic B cell antigen receptor (BCR) stimulation by latent microbial or auto-Ag can trigger the development and expansion of malignant B-cells. The majority of HCL cases display mutated immunoglobulin variable region genes (M-HCL) [22] and a restricted set of BCR with immunoglobulin (Ig) heavy chain variable (V) gene sequences that are identical or stereotyped in subsets of patients [23–27], suggesting that these BCRs bind similar antigens that are relevant to the pathogenesis of HCL. A minority of cases are unmutated (UM-HCL) [22] and apparently more responsive to BCR triggering, whereas the BCR of M-HCL may be less sensitive to stimulation by antigen [22].…”

“…Because of these emerging new therapeutic options it is important to identify patients who may benefit from these new approaches and/or become candidates for treatment at an early stage of their disease. Some data suggest that UM-HCL cells are more responsive to BCR stimulation [22] and hence could be more responsive to therapeutic approaches targeting the BCR.…”