T-cell prolymphocytic leukemia (T-PLL)

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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

Bibliography

Cytogenetic studies on prolymphocytic leukemia. 1. B-cell prolymphocytic leukemia.

Brito-Babapulle V, Pittman S, Melo JV, Pomfret M, Catovsky D

Hematologic pathology. 1987 ; 1 (1) : 27-33.

PMID 3509770

Cytogenetic studies on prolymphocytic leukemia. II. T cell prolymphocytic leukemia.

Brito-Babapulle V, Pomfret M, Matutes E, Catovsky D

Blood. 1987 ; 70 (4) : 926-931.

PMID 3115337

Proposals for the classification of chronic (mature) B and T lymphoid leukaemias. French-American-British (FAB) Cooperative Group.

Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, Sultan C

Journal of clinical pathology. 1989 ; 42 (6) : 567-584.