HAEM5:T-prolymphocytic leukaemia

Haematolymphoid Tumours (5th ed.)

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Primary Author(s)*

Parastou Tizro, MD

WHO Classification of Disease

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Structure	Disease
Book
Category
Family
Type
Subtype(s)

Definition / Description of Disease

T-prolymphocytic leukemia (T-PLL) is a clonal proliferation of small to medium-sized prolymphocytes with a mature post thymic T-cell phenotype characterized by the juxtaposition of TCL1A or MTCP1 to a TR locus, most often the TRA/TRD locus.

Synonyms / Terminology

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Epidemiology / Prevalence

T-PLL is rare, accounting for approximately 2% of cases of mature lymphoid leukemias in adults aged over 30 years. It predominantly affects the elderly (median age: 65 years, range: 30–94 years) with a slight male predominance (M:F ratio: 1.33:1).

Clinical Features

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Signs and Symptoms	Hepatosplenomegaly (Frequently observed) Generalized lymphadenopathy with slightly enlarged lymph nodes (Frequently observed Cutaneous involvement (20%) Malignant effusions (15%) Asymptomatic and indolent phase (30% of cases)
Laboratory Findings	Anaemia and thrombocytopenia Marked lymphocytosis > 100 × 10^9/L (75% of cases) EXAMPLE: Lymphocytosis (low level)

Sites of Involvement

Peripheral blood, bone marrow, spleen, liver, lymph node, and sometimes skin and serosa

Morphologic Features

Blood smears display anemia, thrombocytopenia, and leukocytosis, predominantly of atypical lymphocytes. Bone marrow aspirates show aggregates of neoplastic lymphoid cells.

Immunophenotype

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Finding	Marker
Positive (universal)	CD2, CD3 (may be weak), CD5, CD7
Positive (subset)	CD4 (in some cases CD4+/CD8+ or CD4-/CD8+), CD52
Negative (universal)	TdT, CD1a
Negative (subset)	CD8 (in some cases CD4+/CD8+ or CD4-/CD8+)

Chromosomal Rearrangements (Gene Fusions)

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Chromosomal Rearrangement	Genes in Fusion (5’ or 3’ Segments)	Pathogenic Derivative	Prevalence	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
t(14;14)(q11;q32)	TCL1A/TRD	EXAMPLE: der(22)	EXAMPLE: 20% (COSMIC) EXAMPLE: 30% (add reference)	Yes	EXAMPLE: No	Yes	EXAMPLE: The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
t(X;14)(q28;q11.2)	MTCP1/TRD		Low			Yes

Individual Region Genomic Gain / Loss / LOH

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Chr #	Gain / Loss / Amp / LOH	Minimal Region Genomic Coordinates [Genome Build]	Minimal Region Cytoband	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: 8	EXAMPLE: Gain	EXAMPLE:	EXAMPLE: chr8	EXAMPLE: No	EXAMPLE: No	EXAMPLE: No	EXAMPLE: Common recurrent secondary finding for t(8;21) (add reference).

Characteristic Chromosomal Patterns

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Chromosomal Pattern	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: Co-deletion of 1p and 18q	EXAMPLE: Yes	EXAMPLE: No	EXAMPLE: No	EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

Gene Mutations (SNV / INDEL)

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Gene; Genetic Alteration	Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)	Prevalence (COSMIC / TCGA / Other)	Concomitant Mutations	Mutually Exclusive Mutations	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: TP53; Variable LOF mutations EXAMPLE: EGFR; Exon 20 mutations EXAMPLE: BRAF; Activating mutations	EXAMPLE: TSG	EXAMPLE: 20% (COSMIC) EXAMPLE: 30% (add Reference)	EXAMPLE: IDH1 R123H	EXAMPLE: EGFR amplification	EXAMPLE: Yes	EXAMPLE: No	EXAMPLE: No	EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).

Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Epigenomic Alterations

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Genes and Main Pathways Involved

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Gene; Genetic Alteration	Pathway	Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations	EXAMPLE: MAPK signaling	EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations	EXAMPLE: Cell cycle regulation	EXAMPLE: Unregulated cell division
EXAMPLE: KMT2C and ARID1A; Inactivating mutations	EXAMPLE: Histone modification, chromatin remodeling	EXAMPLE: Abnormal gene expression program

Genetic Diagnostic Testing Methods

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Familial Forms

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Additional Information

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Links

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References

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Notes

*Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.