T-cell prolymphocytic leukemia (T-PLL)

1999-10-01   Martin Yuille 

1.Academic Department of Haematology, Cytogenetics Institute of Cancer Research, 15 Cotswold Road, SUTTON Surrey SM2 5NG, UK
2.Department of Hematology and Center for Human Genetics Cliniques Universitaires Saint Luc Avenue Hippocrate 10 1200 Brussels, Belgium

Clinics and Pathology

Disease

chronic T-cell lymphoproliferative syndrome

Phenotype stem cell 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

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

    • Bibliography

    Pubmed IDLast YearTitleAuthors

    Citation

    Martin Yuille

    T-cell prolymphocytic leukemia (T-PLL)

    Atlas Genet Cytogenet Oncol Haematol. 1999-10-01

    Online version: http://atlasgeneticsoncology.org/haematological/2042/css/lib/bootstrap.min.css

    Historical Card

    1997-10-01 T-cell prolymphocytic leukemia (T-PLL) by  Lucienne Michaux 

    Department of Hematology and Center for Human Genetics Cliniques Universitaires Saint Luc Avenue Hippocrate 10 1200 Brussels, Belgium