Difference between revisions of "HAEM5:T-prolymphocytic leukaemia"
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Revision as of 18:00, 9 May 2024
Haematolymphoid Tumours (5th ed.)
 | This page is under construction |
(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click nearby within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)
Primary Author(s)*
Parastou Tizro, MD
WHO Classification of Disease
(Will be autogenerated; Book will include name of specific book and have a link to the online WHO site)
| Structure | Disease |
|---|---|
| Book | |
| Category | |
| Family | |
| Type | |
| Subtype(s) |
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
Put your text here (Instructions: Include currently used terms and major historical ones, adding “(historical)” after the latter.)
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
Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete table.)
| 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
Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete table.)
| 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)
Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete table.)
| 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 (5%) | Yes |
Individual Region Genomic Gain / Loss / LOH
Put your text here and fill in the table (Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.)
| 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 | Common recurrent secondary finding (70-80% of cases).[1] |
Characteristic Chromosomal Patterns
Put your text here (EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis. Do not delete table.)
| Chromosomal Pattern | Diagnostic Significance (Yes, No or Unknown) | Prognostic Significance (Yes, No or Unknown) | Therapeutic Significance (Yes, No or Unknown) | Notes |
|---|---|---|---|---|
| inv(14)(q11q32) | 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)
Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Do not delete table.)
| 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). |
| TCL1A | Oncogene | ATM mutations | None specified | Yes | Yes | |||
| EZH2 | ||||||||
| FBXW10 | ||||||||
| CHEK2 | ||||||||
| IL2RG | ||||||||
| JAK1 | 20% (COSMIC)
EXAMPLE: 30% (add Reference) |
|||||||
| JAK3 | ||||||||
| STAT5B |
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
Put your text here
Genes and Main Pathways Involved
Put your text here and fill in the table (Instructions: Can include references in the table. Do not delete table.)
| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| EXAMPLE: BRAF and MAP2K1; Activating mutations | EXAMPLE: MAPK signaling | EXAMPLE: Increased cell growth and proliferation |
| TCL1A | AKT signaling | Increased cell survival and proliferation |
| EXAMPLE: KMT2C and ARID1A; Inactivating mutations | EXAMPLE: Histone modification, chromatin remodeling | EXAMPLE: Abnormal gene expression program |
Genetic Diagnostic Testing Methods
The genetic diagnostic process involves detecting clonal rearrangements of the TR gene and rearrangements of the TCL1 gene at the TRB or TRG loci.
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
Put your text here
Links
(use the "Link" icon that looks like two overlapping circles at the top of the page) (Instructions: Highlight text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "http://www." portion.)
References
(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference.)
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.