Difference between revisions of "HAEM5:T-prolymphocytic leukaemia"

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<span style="color:#0070C0">(''General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ 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'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])''</span>
 
<span style="color:#0070C0">(''General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ 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'' </span><u>''[[Author_Instructions]]''</u><span style="color:#0070C0"> ''and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])''</span>
 
==Primary Author(s)*==
 
==Primary Author(s)*==
Parastou Tizro, MD, Sumire Kitahara, MD
+
Parastou Tizro, MD, Celeste Eno, PHD, Sumire Kitahara, MD
 
==WHO Classification of Disease==
 
==WHO Classification of Disease==
 
<span style="color:#0070C0">(Will be autogenerated; Book will include name of specific book and have a link to the online WHO site)</span>
 
<span style="color:#0070C0">(Will be autogenerated; Book will include name of specific book and have a link to the online WHO site)</span>
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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.
 
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==
 
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
+
The most prevalent symptom of the disease is a leukemic presentation, characterized by a rapid, exponential increase in lymphocyte counts, which exceed 100 × 10^9/L in 75% of patients. Approximately 30% of patients may initially experience an asymptomatic, slow-progressing phase, but this typically develops into an active disease state
 
{| class="wikitable"
 
{| class="wikitable"
 
|'''Signs and Symptoms'''
 
|'''Signs and Symptoms'''
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Marked lymphocytosis > 100 × 10^9/L (75% of cases)
 
Marked lymphocytosis > 100 × 10^9/L (75% of cases)
  
Atypical lymphocytosis > 5 × 109/L
+
Atypical lymphocytosis > 5 × 10^9/L  
 
|}
 
|}
 
==Sites of Involvement==
 
==Sites of Involvement==
Peripheral blood, bone marrow, spleen, liver, lymph node, and sometimes skin and serosa
+
Peripheral blood, bone marrow, spleen, liver, lymph node, and sometimes skin and serosa. Extra lymphatic and extramedullary atypical manifestations including skin, muscles and intestines are particularly common in relapse.
 
==Morphologic Features==
 
==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.<ref>{{Cite journal|last=Eichhorn|first=G. L.|date=1979-02|title=Aging, genetics, and the environment: potential of errors introduced into genetic information transfer by metal ions|url=https://pubmed.ncbi.nlm.nih.gov/374897|journal=Mechanisms of Ageing and Development|volume=9|issue=3-4|pages=291–301|doi=10.1016/0047-6374(79)90106-4|issn=0047-6374|pmid=374897}}</ref> Bone marrow aspirates show clusters of these neoplastic cells, with a mixed pattern of involvement including diffuse and interstitial, in trephine core biopsy.
 
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.<ref>{{Cite journal|last=Eichhorn|first=G. L.|date=1979-02|title=Aging, genetics, and the environment: potential of errors introduced into genetic information transfer by metal ions|url=https://pubmed.ncbi.nlm.nih.gov/374897|journal=Mechanisms of Ageing and Development|volume=9|issue=3-4|pages=291–301|doi=10.1016/0047-6374(79)90106-4|issn=0047-6374|pmid=374897}}</ref> Bone marrow aspirates show clusters of these neoplastic cells, with a mixed pattern of involvement including diffuse and interstitial, in trephine core biopsy.
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!Finding!!Marker
 
!Finding!!Marker
 
|-
 
|-
|Positive (universal)||cyTCL1(>90%), CD2, CD3 (may be weak), CD5, CD7
+
|Positive (universal)||cyTCL1(highest specificity), CD2, CD3 (may be weak), CD5, CD7 (strong), TCR-α/β
 
|-
 
|-
|Positive (subset)||CD4 (in some cases CD4+/CD8+ or CD4-/CD8+), CD52
+
|Positive (subset)||CD4 (in some cases CD4+/CD8+ or CD4-/CD8+), CD52, activation markers are variable (CD25, CD38, CD43, CD26, CD27)
 
|-
 
|-
|Negative (universal)||TdT, CD1a
+
|Negative (universal)||TdT, CD1a, CD57, CD16
 
|-
 
|-
 
|Negative (subset)||CD8 (in some cases CD4+/CD8+ or CD4-/CD8+)
 
|Negative (subset)||CD8 (in some cases CD4+/CD8+ or CD4-/CD8+)
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|inv(14)(q11q32)
 
|inv(14)(q11q32)
 
t(14;14)(q11;q32)
 
t(14;14)(q11;q32)
|TCL1A/TRD||<span class="blue-text">EXAMPLE:</span> der(22)||<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
+
|TCL1A/TRD|| ||inv(14) ~60%
<span class="blue-text">EXAMPLE:</span> 30% (add reference)
+
t(14;14) ~25%
 +
|Yes
 
|Yes
 
|Yes
|<span class="blue-text">EXAMPLE:</span> No
 
 
|Yes
 
|Yes
|<span class="blue-text">EXAMPLE:</span>
+
|These genetic abnormalities serve as diagnostic markers and generally indicate an aggressive disease. This is due to their role in overexpressing oncogenes like TCL1A.
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)
 
|t(X;14)(q28;q11.2)
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|}
 
|}
 
==Individual Region Genomic Gain / Loss / LOH==
 
==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.
+
Approximately, 70-80% of T-PLL karyotypes are complex, typically containing 3-5 or more structural aberrations. Common cytogenetic abnormalities include those of chromosome 8, such as idic(8)(p11.2), t(8;8)(p11.2;q12), and trisomy 8q. Other frequent changes are deletions in 12p13 and 22q, gains in 8q24 (MYC), and abnormalities in chromosomes 5p, 6, and 17.
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
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!Therapeutic Significance (Yes, No or Unknown)
 
!Therapeutic Significance (Yes, No or Unknown)
 
!Notes
 
!Notes
|-
 
|11
 
|Loss
 
|11q23.3
 
|ch11
 
|Yes
 
|Yes
 
|Yes
 
|Frequent
 
 
|-
 
|-
 
|8
 
|8
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|No
 
|No
 
|No
 
|No
|Recurrent secondary finding (70-80% of cases).<ref>{{Cite journal|last=Matutes|first=E.|last2=Brito-Babapulle|first2=V.|last3=Swansbury|first3=J.|last4=Ellis|first4=J.|last5=Morilla|first5=R.|last6=Dearden|first6=C.|last7=Sempere|first7=A.|last8=Catovsky|first8=D.|date=1991-12-15|title=Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/1742486|journal=Blood|volume=78|issue=12|pages=3269–3274|issn=0006-4971|pmid=1742486}}</ref>
+
|Recurrent secondary finding <ref>{{Cite journal|last=Matutes|first=E.|last2=Brito-Babapulle|first2=V.|last3=Swansbury|first3=J.|last4=Ellis|first4=J.|last5=Morilla|first5=R.|last6=Dearden|first6=C.|last7=Sempere|first7=A.|last8=Catovsky|first8=D.|date=1991-12-15|title=Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/1742486|journal=Blood|volume=78|issue=12|pages=3269–3274|issn=0006-4971|pmid=1742486}}</ref>
 +
|-
 +
|11
 +
|Loss
 +
|11q23.3
 +
|ch11
 +
|Yes
 +
|Yes
 +
|Yes
 +
|Frequent
 
|-
 
|-
 
|5
 
|5
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|
 
|
 
|-
 
|-
|''IL2RG''
+
|''JAK1, JAK3, STAT5b, IL2RG''
 
|
 
|
 
|
 
|
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|Increased cell survival and proliferation
 
|Increased cell survival and proliferation
 
|-
 
|-
|<span class="blue-text">EXAMPLE:</span>s
+
|''JAK1, JAK3, STAT5b, IL2RG''
|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling
+
|JAk-STAT pathway
 
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
 
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program
 
|}
 
|}
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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.<ref>{{Cite journal|last=Suarez|first=Felipe|last2=Mahlaoui|first2=Nizar|last3=Canioni|first3=Danielle|last4=Andriamanga|first4=Chantal|last5=Dubois d'Enghien|first5=Catherine|last6=Brousse|first6=Nicole|last7=Jais|first7=Jean-Philippe|last8=Fischer|first8=Alain|last9=Hermine|first9=Olivier|date=2015-01-10|title=Incidence, presentation, and prognosis of malignancies in ataxia-telangiectasia: a report from the French national registry of primary immune deficiencies|url=https://pubmed.ncbi.nlm.nih.gov/25488969|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=33|issue=2|pages=202–208|doi=10.1200/JCO.2014.56.5101|issn=1527-7755|pmid=25488969}}</ref> Penetrance of the tumor phenotype is about 10% to 15% by early adulthood.<ref>{{Cite journal|last=Taylor|first=A. M.|last2=Metcalfe|first2=J. A.|last3=Thick|first3=J.|last4=Mak|first4=Y. F.|date=1996-01-15|title=Leukemia and lymphoma in ataxia telangiectasia|url=https://pubmed.ncbi.nlm.nih.gov/8555463|journal=Blood|volume=87|issue=2|pages=423–438|issn=0006-4971|pmid=8555463}}</ref> It represents nearly 3% of all malignancies in patients with ataxia-telangiectasia.<ref>{{Cite journal|last=Li|first=Geling|last2=Waite|first2=Emily|last3=Wolfson|first3=Julie|date=2017-12-26|title=T-cell prolymphocytic leukemia in an adolescent with ataxia-telangiectasia: novel approach with a JAK3 inhibitor (tofacitinib)|url=https://pubmed.ncbi.nlm.nih.gov/29296924|journal=Blood Advances|volume=1|issue=27|pages=2724–2728|doi=10.1182/bloodadvances.2017010470|issn=2473-9529|pmc=5745136|pmid=29296924}}</ref>
 
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.<ref>{{Cite journal|last=Suarez|first=Felipe|last2=Mahlaoui|first2=Nizar|last3=Canioni|first3=Danielle|last4=Andriamanga|first4=Chantal|last5=Dubois d'Enghien|first5=Catherine|last6=Brousse|first6=Nicole|last7=Jais|first7=Jean-Philippe|last8=Fischer|first8=Alain|last9=Hermine|first9=Olivier|date=2015-01-10|title=Incidence, presentation, and prognosis of malignancies in ataxia-telangiectasia: a report from the French national registry of primary immune deficiencies|url=https://pubmed.ncbi.nlm.nih.gov/25488969|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=33|issue=2|pages=202–208|doi=10.1200/JCO.2014.56.5101|issn=1527-7755|pmid=25488969}}</ref> Penetrance of the tumor phenotype is about 10% to 15% by early adulthood.<ref>{{Cite journal|last=Taylor|first=A. M.|last2=Metcalfe|first2=J. A.|last3=Thick|first3=J.|last4=Mak|first4=Y. F.|date=1996-01-15|title=Leukemia and lymphoma in ataxia telangiectasia|url=https://pubmed.ncbi.nlm.nih.gov/8555463|journal=Blood|volume=87|issue=2|pages=423–438|issn=0006-4971|pmid=8555463}}</ref> It represents nearly 3% of all malignancies in patients with ataxia-telangiectasia.<ref>{{Cite journal|last=Li|first=Geling|last2=Waite|first2=Emily|last3=Wolfson|first3=Julie|date=2017-12-26|title=T-cell prolymphocytic leukemia in an adolescent with ataxia-telangiectasia: novel approach with a JAK3 inhibitor (tofacitinib)|url=https://pubmed.ncbi.nlm.nih.gov/29296924|journal=Blood Advances|volume=1|issue=27|pages=2724–2728|doi=10.1182/bloodadvances.2017010470|issn=2473-9529|pmc=5745136|pmid=29296924}}</ref>
 
==Additional Information==
 
==Additional Information==
Put your text here
+
In T-PLL, the rapid growth of the disease necessitates immediate initiation of treatment. The most effective first-line treatment is alemtuzumab, an anti-CD52 antibody with remission rates over 80%. However, these remissions usually last only 1-2 years. To potentially extend remission, eligible patients are advised to undergo allogeneic blood stem cell transplantation (allo-SCT) during their first complete remission, which can lead to longer remission durations of over 4-5 years for 15-30% of patients. Consequently, the prognosis for T-PLL remains poor, with median overall survival times under two years and five-year survival rates below 5%[https://clinicaltrials.gov/study/NCT03989466 . Ongoing research is exploring molecularly targeted drugs and signaling pathway inhibitors, for routine clinical use in treating T-PLL.]
 
==Links==
 
==Links==
 
(use the "Link" icon that looks like two overlapping circles at the top of the page) <span style="color:#0070C0">(''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 "<nowiki>http://www</nowiki>." portion.'')</span>
 
(use the "Link" icon that looks like two overlapping circles at the top of the page) <span style="color:#0070C0">(''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 "<nowiki>http://www</nowiki>." portion.'')</span>

Revision as of 20:26, 9 May 2024


Haematolymphoid Tumours (5th ed.)

(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, Celeste Eno, PHD, 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

The most prevalent symptom of the disease is a leukemic presentation, characterized by a rapid, exponential increase in lymphocyte counts, which exceed 100 × 10^9/L in 75% of patients. Approximately 30% of patients may initially experience an asymptomatic, slow-progressing phase, but this typically develops into an active disease state

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 × 10^9/L

Sites of Involvement

Peripheral blood, bone marrow, spleen, liver, lymph node, and sometimes skin and serosa. Extra lymphatic and extramedullary atypical manifestations including skin, muscles and intestines are particularly common in relapse.

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

Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete table.)

Finding Marker
Positive (universal) cyTCL1(highest specificity), CD2, CD3 (may be weak), CD5, CD7 (strong), TCR-α/β
Positive (subset) CD4 (in some cases CD4+/CD8+ or CD4-/CD8+), CD52, activation markers are variable (CD25, CD38, CD43, CD26, CD27)
Negative (universal) TdT, CD1a, CD57, CD16
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
inv(14)(q11q32)

t(14;14)(q11;q32)

TCL1A/TRD inv(14) ~60%

t(14;14) ~25%

Yes Yes Yes These genetic abnormalities serve as diagnostic markers and generally indicate an aggressive disease. This is due to their role in overexpressing oncogenes like TCL1A.
t(X;14)(q28;q11.2) MTCP1/TRD Low (5%) Yes

Individual Region Genomic Gain / Loss / LOH

Approximately, 70-80% of T-PLL karyotypes are complex, typically containing 3-5 or more structural aberrations. Common cytogenetic abnormalities include those of chromosome 8, such as idic(8)(p11.2), t(8;8)(p11.2;q12), and trisomy 8q. Other frequent changes are deletions in 12p13 and 22q, gains in 8q24 (MYC), and abnormalities in chromosomes 5p, 6, and 17.

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
8q24 (MYC)

chr8 Yes No No Recurrent secondary finding [2]
11 Loss 11q23.3 ch11 Yes Yes Yes Frequent
5
14 Loss 14q chr14 In approximately (37%)
12 Loss 12p13 chr12

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) 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
JAK1, JAK3, STAT5b, 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
TCL1A AKT signaling and TCR signal amplification pathways Increased cell survival and proliferation
JAK1, JAK3, STAT5b, IL2RG JAk-STAT pathway 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

In T-PLL, the rapid growth of the disease necessitates immediate initiation of treatment. The most effective first-line treatment is alemtuzumab, an anti-CD52 antibody with remission rates over 80%. However, these remissions usually last only 1-2 years. To potentially extend remission, eligible patients are advised to undergo allogeneic blood stem cell transplantation (allo-SCT) during their first complete remission, which can lead to longer remission durations of over 4-5 years for 15-30% of patients. Consequently, the prognosis for T-PLL remains poor, with median overall survival times under two years and five-year survival rates below 5%. Ongoing research is exploring molecularly targeted drugs and signaling pathway inhibitors, for routine clinical use in treating T-PLL.

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References

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Notes

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  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.