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 |
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| Book | |
| Category | |
| Family | |
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Definition / Description of Disease
T-prolymphocytic leukemia (T-PLL) is an aggressive form of T-cell leukemia marked by the proliferation of small to medium-sized prolymphocytes exhibiting a mature post-thymic T-cell phenotype. This condition is characterized by the juxtaposition of TCL1A or MTCP1 genes to a TR locus, typically the TRA/TRD locus.
Synonyms / Terminology
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Epidemiology / Prevalence
T-PLL is a rare disorder, comprising about 2% of all mature lymphoid leukemia cases in adults. It primarily occurs in the elderly, with a median age of 65 years (ranging from 30 to 94 years), and shows a slight male predominance with a male to female ratio of 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) |
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 |
|---|---|---|---|---|---|---|---|
| inv(14)(q11q32)
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 (5%) | 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 |
|---|---|---|---|---|---|---|---|
| 8 | Gain | idic(8)(p11.2)
t(8;8)(p11.2;q12) trisomy 8q |
chr8 | No | No | No | EXAMPLE:
Common recurrent secondary finding (70-80% of cases).[1] |
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
A subset of cases may develop in the context of ataxia-telangiectasia (AT), which is characterized by germline mutations in the ATM gene. Penetrance of the tumor phenotype is about 10% to 15% by early adulthood.[2] It represents nearly 3% of all malignancies in patients with ataxia-telangiectasia.[3]
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.
- ↑ Matutes, E.; et al. (1991-12-15). "Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia". Blood. 78 (12): 3269–3274. ISSN 0006-4971. PMID 1742486.
- ↑ Taylor, A. M.; et al. (1996-01-15). "Leukemia and lymphoma in ataxia telangiectasia". Blood. 87 (2): 423–438. ISSN 0006-4971. PMID 8555463.
- ↑ Li, Geling; et al. (2017-12-26). "T-cell prolymphocytic leukemia in an adolescent with ataxia-telangiectasia: novel approach with a JAK3 inhibitor (tofacitinib)". Blood Advances. 1 (27): 2724–2728. doi:10.1182/bloodadvances.2017010470. ISSN 2473-9529. PMC 5745136. PMID 29296924.