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T-cell prolymphocytic leukemia (T-PLL)

Written1999-10Martin Yuille
Academic Department of Haematology, Cytogenetics Institute of Cancer Research, 15 Cotswold Road, SUTTON Surrey SM2 5NG, UK
This article is an update of :
1997-10Lucienne Michaux
Department of Hematology and Center for Human Genetics Cliniques Universitaires Saint Luc Avenue Hippocrate 10 1200 Brussels, Belgium

(Note : for Links provided by Atlas : click)


ICD-Morpho 9834/3 T-cell prolymphocytic leukaemia
Atlas_Id 2042

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 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

  • 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
  • Bibliography

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    Biallelic mutations in the ATM gene in T-prolymphocytic leukemia.
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    Inactivation of the ATM gene in T-cell prolymphocytic leukemias.
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    A gene on chromosome Xq28 associated with T-cell prolymphocytic leukemia in two patients with ataxia telangiectasia.
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    Chromosome walking on the TCL1 locus involved in T-cell neoplasia.
    Virgilio L, Isobe M, Narducci MG, Carotenuto P, Camerini B, Kurosawa N, Abbas-ar-Rushdi, Croce CM, Russo G
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    Clustering of missense mutations in the ataxia-telangiectasia gene in a sporadic T-cell leukaemia.
    Vorechovský I, Luo L, Dyer MJ, Catovsky D, Amlot PL, Yaxley JC, Foroni L, Hammarström L, Webster AD, Yuille MA
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    ATM is usually rearranged in T-cell prolymphocytic leukaemia.
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    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 journal version : [ pdf ]   [ DOI ]
    On line version :
    History of this paper:
    Michaux, L. T-cell prolymphocytic leukemia (T-PLL). Atlas Genet Cytogenet Oncol Haematol. 1997;1(2):83-84.

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


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