T-prolymphocytic leukaemia


Haematolymphoid Tumours (5th ed.)

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Primary Author(s)*

Parastou Tizro, MD, Sumire Kitahara, 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

T-cell chronic lymphocytic leukemia

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 B symptoms (Fever, night sweats, weight loss)

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 Anemia and thrombocytopenia

Marked lymphocytosis > 100 × 10^9/L (75% of cases)

Atypical lymphocytosis > 5 × 109/L

Sites of Involvement

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

Morphologic Features

Blood smears in T-PLL typically reveal anemia, thrombocytopenia, and leukocytosis, with atypical lymphocytes in three morphological forms. The most common form (75% of cases) features medium-sized cells with a high nuclear-to-cytoplasmic ratio, moderately condensed chromatin, a single visible nucleolus, and slightly basophilic cytoplasm with characteristic cytoplasmic blebs. In 20% of cases, the cells appear as a small cell variant with densely condensed chromatin and an inconspicuous nucleolus. About 5% of cases exhibit a cerebriform variant with irregular nuclei resembling those in mycosis fungoides.[1] Bone marrow aspirates show clusters of these neoplastic cells, with a mixed pattern of involvement including diffuse and interstitial, in trephine core biopsy.

Immunophenotype

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Finding Marker
Positive (universal) cyTCL1(>90%), 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

In T-cell prolymphocytic leukemia (T-PLL), complex karyotypes are commonly observed in 70–80% of cases. Frequent cytogenetic abnormalities include abnormalities of chromosome 8 such as idic(8)(p11.2), t(8;8)(p11.2;q12), and trisomy 8q, present in 70–80% of cases (PMID: 10077617). Additionally, deletions in 12p13 (PMID: 11920168) and 22q (PMID: 19480937), gains in 8q24 (MYC) (PMID: 25310835), and abnormalities of chromosomes 5p, 6, and 17 (PMID: 1913594; 14580769; 19278963) are also noted. These genetic alterations contribute to the pathophysiology and diagnostic complexity of T-PLL.

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
11 Loss 11q23.3 ch11 Yes Yes Yes Frequent
8 Gain idic(8)(p11.2)

t(8;8)(p11.2;q12)

trisomy 8q
8q24 (MYC)

chr8 Yes No No Recurrent secondary finding (70-80% of cases).[2]
5
14 Loss 14q chr14 In approximately (37%)
12 Loss 12p13 chr12

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
inv(14)(q11q32) 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).
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

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Genes and Main Pathways Involved

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Gene; Genetic Alteration Pathway Pathophysiologic Outcome
TCL1A AKT signaling and TCR signal amplification pathways Increased cell survival and proliferation
EXAMPLE:s EXAMPLE: Histone modification, chromatin remodeling EXAMPLE: Abnormal gene expression program

Genetic Diagnostic Testing Methods

Cytogenetics (FISH, CpG-stimulated Karyotype, SNP microarray), PCR for TRB/TRG and Next-Generation Sequencing (NGS). 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

There is no noticeable familial clustering. However, a subset of cases may develop in the context of ataxia-telangiectasia (AT), which is characterized by germline mutations in the ATM gene. Here there is a combined heterozygosity in the form of biallelic inactivating mutations of the ATM tumor suppressor gene.[3] Penetrance of the tumor phenotype is about 10% to 15% by early adulthood.[4] It represents nearly 3% of all malignancies in patients with ataxia-telangiectasia.[5]

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.

  1. Eichhorn, G. L. (1979-02). "Aging, genetics, and the environment: potential of errors introduced into genetic information transfer by metal ions". Mechanisms of Ageing and Development. 9 (3–4): 291–301. doi:10.1016/0047-6374(79)90106-4. ISSN 0047-6374. PMID 374897. Check date values in: |date= (help)
  2. 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.
  3. Suarez, Felipe; et al. (2015-01-10). "Incidence, presentation, and prognosis of malignancies in ataxia-telangiectasia: a report from the French national registry of primary immune deficiencies". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 33 (2): 202–208. doi:10.1200/JCO.2014.56.5101. ISSN 1527-7755. PMID 25488969.
  4. Taylor, A. M.; et al. (1996-01-15). "Leukemia and lymphoma in ataxia telangiectasia". Blood. 87 (2): 423–438. ISSN 0006-4971. PMID 8555463.
  5. 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.