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T-cell prolymphocytic leukemia (T-PLL)

Clinics and Pathology

Disease chronic T-cell lymphoproliferative syndrome
Phenotype / cell stem origin disease affecting mature T-cells; T-cell prolymphocytes usually express CD3, CD5 and CD7; they have either a T-helper (CD4+/CD8-) or a T-suppressor (CD4-/CD8+) phenotype; a small number of cases may co-express CD4 and CD8; this finding is more prevalent in the small cell variant of T-PLL than in classic T-PLL
Epidemiology very rare disease; represents 20% of prolymphocytic leukemias; the disease occurs at advanced age, typically in the 7th or 8th decade; slight male predominance
Clinics splenomegaly is common; lymphadenopathy at presentation is unusual but more frequent than in B-PLL; blood data: high leucocyte counts usually exceeding 100x109/l; T-cell prolymphocytes have the same morphologic features than B-cell prolymphocytes; a small cell variant of T-PLL has been described
Prognosis evolution: progresses rapidly and is generally more aggressive than B-PLL; prognosis: poor response to chemotherapy is observed; median survival is approximatively 7 months from diagnosis

Cytogenetics

Cytogenetics Morphological few cases have been reported in the literature
  • so far; karyotypes are usually complex
  • 14q11 abnormalities: very frequent, either as an inv(14)(q11q32) or as a translocation t(14;14)(q11;q32); another reported change involving 14q11 is a translocation t(X;14)(q28;q11), similar to the translocation observed in ataxia-telangectasia, involving the Mature T-cell Prolymphocyte 1 (MTCP1) gene located at Xq28
  • other recurrent changes involve chromosome 8 either as i(8)(q10) or as der(8) t(8;8)
  • finally, some aberrations involving 12p have been reported
  • Genes involved and Proteins

    Note
  • as with other T-cell neoplasms, T-PLL exhibits clonal rearrangement of T-cell receptor genes; translocation t(X;14)(q28;q11) may result into fusion of MTCP1 with TRA/Dgenes; finally, the TCL1 locus on chromosome 14q32 might also been involved
  • in Ataxia Telangiectasia- a rare recessive pleiotropic disease (including elevated cancer predisposition) mapping to 11q23 and caused by mutations of theATM gene - a recurrent malignancy is observed that is similar to T-PLL; its frequency in A-T patients is higher than in the non-A-T related form; A-T related TPLL has a similar course, a similar immunophenotype and similar cytogenetics (with the notable exception that 11q23 breakpoints are recurrent in the sporadic but not the A-T related form of the disease); an initial report of ATM mutations in T-PLL demonstrated the principle that ATM was a candidate cancer gene in sporadic forms of malignancies prevalent in A-T; the identification of lesions in ATM associated with T-PLL has shown that:
  • homozygous truncating mutations are present in some cases; this suggests ATM can appear to act like a conventional tumour suppressor with biallelic inactivation in the tumour cell
  • missense mutations cluster in the carboxy-terminal phosphatidyl-3-kinase (PIK) domain; this suggests impairment of this domain can contribute to - and may constitute a distinct step in - tumourigenesis
  • rearrangement of the gene is frequent; some rearrangements are consistent with a translocation event, in agreement with cytogenetic data implicating 11q23 in T-PLL; others involve transposition of a segment of the ATM gene elsewhere in the genome.
  • one allele only is mutated (by rearrangement) in some cases; this is probably not associated with a concomitant epigenetic event such as abnormal promoter methylation
  • no T-PLL case has been reported with germline ATM mutation; this may reflect the small numbers investigated; all the same, the hypothesis is excluded that this rare disease is due solely to germline ATM mutation
  • Other genes implicated (Data extracted from papers in the Atlas)

    Genes ATM MTCP1 SOX11 SOX4 TCL1B TCL1A TCL1A TRA TRD

    Translocations implicated (Data extracted from papers in the Atlas)

    Bibliography

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    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed

    Contributor(s)

    Written10-1997Lucienne Michaux
    Updated10-1999Martin Yuille

    Citation

    This paper should be referenced as such :
    Yuille, M
    T-cell prolymphocytic leukemia (T-PLL)
    Atlas Genet Cytogenet Oncol Haematol. 1999;3(4):187-188.
    Free online version   Free pdf version   [Bibliographic record ]
    Atlas Genet Cytogenet Oncol Haematol. October 1997
    http://documents.irevues.inist.fr/bitstream/handle/2042/32064/10-1997-TPLL.pdf
    URL : http://AtlasGeneticsOncology.org/Anomalies/TPLL.html

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    indexed on : Sat Jul 26 14:19:26 CEST 2014


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