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

2000-10-01   Estella Matutes  , Daniel Catovsky  , Vasantha Brito-Babapulle  

1.Academic Department of Haematology, Cytogenetics, The Royal Marsden NHS Trust, London, UK

Clinics and Pathology

Phenotype stem cell 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.

Prognosis

  • 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

    Genes Involved and Proteins

    Note
  • 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.

    • Article Bibliography

    Pubmed IDLast YearTitleAuthors
    85471151995Increased expression of the PRAD-1/CCND1 gene in hairy cell leukaemia.Bosch F et al
    75220431994Chromosome abnormalities in hairy cell leukaemia variant.Brito-Babapulle V et al
    86184401996Cloning and characterization of the human tartrate-resistant acid phosphatase (TRAP) gene.Fleckenstein E et al
    7179401978Hairy cell leukemia: a clinical review based on 71 cases.Golomb HM et al
    81673431994Hairy cell leukemia is characterized by clonal chromosome abnormalities clustered to specific regions.Haglund U et al
    78200521994Aberrant rearrangements within the immunoglobulin heavy chain locus in hairy cell leukemia.Kayano H et al
    78200541994The 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 et al
    112433882001The natural history and clinico-pathological features of the variant form of hairy cell leukemia.Matutes E et al
    84680461993Human lymphocyte-specific pp52 gene is a member of a highly conserved dispersed family.May W et al
    23641671990A variant form of hairy cell leukemia resistant to alpha-interferon: clinical and phenotypic characteristics of 17 patients.Sainati L et al
    105765091999p53 gene deletion and trisomy 12 in hairy cell leukemia and its variant.Vallianatou K et al
    93324721997Hairy cell leukemia variant with t(2;8)(p12;q24) abnormality.Wong KF et al
    87407881996Involvement of the CCND1 gene in hairy cell leukemia.de Boer CJ et al

    Citation

    Estella Matutes ; Daniel Catovsky ; Vasantha Brito-Babapulle

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

    Atlas Genet Cytogenet Oncol Haematol. 2000-10-01

    Online version: http://atlasgeneticsoncology.org/haematological/2036/hairy-cell-leukemia-(hcl)-and-hairy-cell-leukemia-variant-(hcl-v)