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Hairy Cell Leukemia (HCL) and Hairy Cell Leukemia Variant (HCL-V)

Written2000-10Vasantha Brito-Babapulle, Estella Matutes , Daniel Catovsky
Academic Department of Haematology, Cytogenetics, The Royal Marsden NHS Trust, London, UK

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ICD-Morpho 9940/3 Hairy cell leukaemia
Atlas_Id 2036

Clinics and Pathology

Phenotype / cell stem origin cells from hairy cell leukemia (HCL) and hairy cell leukemia variant (HCL-V) have a distinct immunophenotype which is of a mature but not terminally differentiated activated B-cell. Although some similarities exist between these two conditions like the expression of B-cell activation marker CD103, CD11c and IgG heavy chain expression, differences exists between these two diseases. HCL is positive for CD25 (anti IL2 receptor) and HC2 while HCL-V is negative for CD25 and HC2.
Epidemiology first described as leukaemic reticulo endotheliosis, HCL predominantly affects middle aged males (male /female ratio = 4) while male predominance is not observed in HCL-V but they are older
Clinics HCL patients present with splenomegaly, cytopenia(s) and variable proportions of circulating hairy cells. Monocytopenia is constant, lymphadenopathy is rare and the bone marrow is "dry tap" in most cases. HCL-V patients show most of the above features but have high white blood cell counts normal numbers of monocytes and aspirable bone marrow.
Cytology The typical hairy cell is large in size, has an eccentric and sometimes kidney shaped nucleus and abundant cytoplasm with long villi which is associated with alterations in the cytoskeletal architecture. HCL-V has a central round nucleus, a prominent nucleolus, cytoplasmic villi and is intermediate in morphology between HCL and B-prolymphocytic leukaemia. HCL cells show strong acid phosphatase reaction which is resistant to tartaric acid.
Pathology The bone marrow and spleen histology is identical in HCL and HCL-V. The bone marrow shows a distinct pattern of interstital infiltration by lymphoid cells with spaces among them ('fried egg ' pattern). Reticulin is invariably increased in HCL but not in HCL-V. Spleen histology shows expansion and infiltration of the red pulp with naked white pulp.
Treatment Interferon alpha produces good partial responses in HCL but invariably the disease relapses. The purine analogs 2 deoxycorformycin and 2-deoxyadenosine induce responses in >95% of patients, most of them complete and durable. HCL-V is not responsive to the above treatments with only half achieving transient partial responses to the purine analogs with splenectomy being the best palliative therapeutic measure.
Evolution HCL and HCL-V are characterised by a chronic clinical course with the symptoms deriving from cytopenias, and abdominal distension due to splenomegaly. Few patients undergo transformation.
  • HCL has a good prognosis .In a large series 80% of patients survived at 12 years.
  • HCL -V has a poorer prognosis and in the only largest series reported the median survival is 9 years.
  • Cytogenetics

    Cytogenetics Morphological
  • Several reports describe nonclonal or oligoclonal abnormalities in HCL and in some with clonal abnormalities translocations involving the 14q32.3 the site of the IGH locus, rearrangements of 14q22-24 and abnormalities of chromosomes 11 and 12 have been described. One study reported a 40% incidence of chromosome 5 abnormalities.
  • HCL-V is often characterised by a complex karyotype. Translocation t(14;18)(q32;q21) observed in follicular lymphoma and t(2;8)(p12;q24) observed in variant Burkitt lymphoma have been reported in HCL-V.
  • Cytogenetics Molecular Deletion of the p53 tumour suppressor gene mapping to chromosome 17p13 occurs with a high incidence in both HCL and HCL-V. But a significant difference is observed in the proportion of cells with a deleted allele in HCL-V compared to HCL(P<0.01) and correlates with the well known tendency for transformation and poor response to therapy characteristic of HCL-V

    Genes involved and Proteins

  • Molecular studies suggest that hairy cells have aberrations in the constant region of the IgM intron which could be responsible for errors in class switching and explain the pattern of Ig heavy chain expression in HCL which does not fit the the class switching model which occurs in normal B-cell differentiation.
  • Over expression of the BCL-1 gene on chromosome 11q13 and encoding Cyclin D-1 has been demonstrated by Northern blot for RNA and Western blot and immunocytochemistry for protein expression in over 70% of patients with HCL investigated (including 1HCL-V), but with no evidence for chromosomal or molecular rearrangement of the BCL-1 locus.
  • The steady state m-RNA and protein levels of the leucocyte specific gene pp52 coding for a cytoskeletal protein and binding to filamentous actin (F-actin) is elevated in HCL.The gene maps to chromosome 11p15.5. Colocalisation of pp52 with F-actin occurs at the base of the villi. Interferon alpha (IFN alpha) a highly effective agent in the treatment of HCL has been shown to reduce pp52 m- RNA and blunt the villi.
  • Bibliography

    Hairy cell leukemia. Advances in Blood Disorders.
    Tallman MS and Polliack A Eds..
    Increased expression of the PRAD-1/CCND1 gene in hairy cell leukaemia.
    Bosch F, Campo E, Jares P, Pittaluga S, Muñoz J, Nayach I, Piris MA, Dewolf-Peeters C, Jaffe ES, Rozman C
    British journal of haematology. 1995 ; 91 (4) : 1025-1030.
    PMID 8547115
    Chromosome abnormalities in hairy cell leukaemia variant.
    Brito-Babapulle V, Matutes E, Oscier D, Mould S, Catovsky D
    Genes, chromosomes & cancer. 1994 ; 10 (3) : 197-202.
    PMID 7522043
    Cloning and characterization of the human tartrate-resistant acid phosphatase (TRAP) gene.
    Fleckenstein E, Dirks W, Dehmel U, Drexler HG
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1996 ; 10 (4) : 637-643.
    PMID 8618440
    Hairy cell leukemia: a clinical review based on 71 cases.
    Golomb HM, Catovsky D, Golde DW
    Annals of internal medicine. 1978 ; 89 (5 Pt 1) : 677-683.
    PMID 717940
    Hairy cell leukemia is characterized by clonal chromosome abnormalities clustered to specific regions.
    Haglund U, Juliusson G, Stellan B, Gahrton G
    Blood. 1994 ; 83 (9) : 2637-2645.
    PMID 8167343
    Aberrant rearrangements within the immunoglobulin heavy chain locus in hairy cell leukemia.
    Kayano H, Dyer MJ, Zani VJ, Laffan MA, Matutes E, Asou N, Katayama I, Catovsky D
    Leukemia & lymphoma. 1994 ; 14 Suppl 1 : 41-47.
    PMID 7820052
    The immunophenotype of hairy cell leukemia (HCL). Proposal for a scoring system to distinguish HCL from B-cell disorders with hairy or villous lymphocytes.
    Matutes E, Morilla R, Owusu-Ankomah K, Houliham A, Meeus P, Catovsky D
    Leukemia & lymphoma. 1994 ; 14 Suppl 1 : 57-61.
    PMID 7820054
    The natural history and clinico-pathological features of the variant form of hairy cell leukemia.
    Matutes E, Wotherspoon A, Brito-Babapulle V, Catovsky D
    Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2001 ; 15 (1) : 184-186.
    PMID 11243388
    Human lymphocyte-specific pp52 gene is a member of a highly conserved dispersed family.
    May W, Korenberg JR, Chen XN, Lunsford L, Wood WJ, Thompson A, Wall R, Denny CT
    Genomics. 1993 ; 15 (3) : 515-520.
    PMID 8468046
    Aberrant Expression of leucocyte specific pp52 in hairy cell leukemia (Meeting abstract ).
    Miyoshi E, Wall R, Thompson AA
    A variant form of hairy cell leukemia resistant to alpha-interferon: clinical and phenotypic characteristics of 17 patients.
    Sainati L, Matutes E, Mulligan S, de Oliveira MP, Rani S, Lampert IA, Catovsky D
    Blood. 1990 ; 76 (1) : 157-162.
    PMID 2364167
    p53 gene deletion and trisomy 12 in hairy cell leukemia and its variant.
    Vallianatou K, Brito-Babapulle V, Matutes E, Atkinson S, Catovsky D
    Leukemia research. 1999 ; 23 (11) : 1041-1045.
    PMID 10576509
    Hairy cell leukemia variant with t(2;8)(p12;q24) abnormality.
    Wong KF, Kwong YL, Hui PK
    Cancer genetics and cytogenetics. 1997 ; 98 (2) : 102-105.
    PMID 9332472
    Involvement of the CCND1 gene in hairy cell leukemia.
    de Boer CJ, Kluin-Nelemans JC, Dreef E, Kester MG, Kluin PM, Schuuring E, van Krieken JH
    Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 1996 ; 7 (3) : 251-256.
    PMID 8740788


    This paper should be referenced as such :
    Brito-Babapulle, V ; Matutes, E ; Catovsky, D
    Hairy cell leukemia (HCL), hairy cell leukemia variant (HCL-V)
    Atlas Genet Cytogenet Oncol Haematol. 2000;4(4):203-204.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

    Other genes implicated (Data extracted from papers in the Atlas) [ 8 ]


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