Difference between revisions of "HAEM5:Early T-precursor lymphoblastic leukaemia / lymphoma"
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{{DISPLAYTITLE:Early T-precursor lymphoblastic leukaemia / lymphoma}} | {{DISPLAYTITLE:Early T-precursor lymphoblastic leukaemia / lymphoma}} | ||
| − | [[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]] | + | [[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]] |
{{Under Construction}} | {{Under Construction}} | ||
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}}</blockquote> | }}</blockquote> | ||
| − | <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). 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)*== | ||
| Line 43: | Line 43: | ||
==Clinical Features== | ==Clinical Features== | ||
| − | Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span> | + | 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> |
{| class="wikitable" | {| class="wikitable" | ||
|'''Signs and Symptoms''' | |'''Signs and Symptoms''' | ||
| − | |EXAMPLE Asymptomatic (incidental finding on complete blood counts) | + | |<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts) |
| − | EXAMPLE B-symptoms (weight loss, fever, night sweats) | + | <span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats) |
| − | EXAMPLE Fatigue | + | <span class="blue-text">EXAMPLE:</span> Fatigue |
| − | EXAMPLE Lymphadenopathy (uncommon) | + | <span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon) |
|- | |- | ||
|'''Laboratory Findings''' | |'''Laboratory Findings''' | ||
| − | |EXAMPLE Cytopenias | + | |<span class="blue-text">EXAMPLE:</span> Cytopenias |
| − | EXAMPLE Lymphocytosis (low level) | + | <span class="blue-text">EXAMPLE:</span> Lymphocytosis (low level) |
|} | |} | ||
| − | <blockquote class='blockedit'>{{Box-round|title= | + | <blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|The content below was from the previous version of the page. Please incorporate above.}} |
The clinical features of ETP-ALL are similar to that of other subtypes of T-ALL, including a high leukocyte count, anterior mediastinal mass or other tissue mass, lymphadenopathy, hepatosplenomegaly<ref name=":3">{{Cite journal|last=Inukai|first=Takeshi|last2=Kiyokawa|first2=Nobutaka|last3=Campana|first3=Dario|last4=Coustan-Smith|first4=Elaine|last5=Kikuchi|first5=Akira|last6=Kobayashi|first6=Miyuki|last7=Takahashi|first7=Hiroyuki|last8=Koh|first8=Katsuyoshi|last9=Manabe|first9=Atsushi|date=2012-02|title=Clinical significance of early T-cell precursor acute lymphoblastic leukaemia: results of the Tokyo Children's Cancer Study Group Study L99-15|url=https://pubmed.ncbi.nlm.nih.gov/22128890|journal=British Journal of Haematology|volume=156|issue=3|pages=358–365|doi=10.1111/j.1365-2141.2011.08955.x|issn=1365-2141|pmid=22128890}}</ref><ref name=":4">Borowitz MJ, et al., (2016).T-lymphoblastic leukemia/lymphoma, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4thedition.Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p176-178.</ref>. Some patients who develop an anterior mediastinal mass can lead to superior vena cava syndrome. | The clinical features of ETP-ALL are similar to that of other subtypes of T-ALL, including a high leukocyte count, anterior mediastinal mass or other tissue mass, lymphadenopathy, hepatosplenomegaly<ref name=":3">{{Cite journal|last=Inukai|first=Takeshi|last2=Kiyokawa|first2=Nobutaka|last3=Campana|first3=Dario|last4=Coustan-Smith|first4=Elaine|last5=Kikuchi|first5=Akira|last6=Kobayashi|first6=Miyuki|last7=Takahashi|first7=Hiroyuki|last8=Koh|first8=Katsuyoshi|last9=Manabe|first9=Atsushi|date=2012-02|title=Clinical significance of early T-cell precursor acute lymphoblastic leukaemia: results of the Tokyo Children's Cancer Study Group Study L99-15|url=https://pubmed.ncbi.nlm.nih.gov/22128890|journal=British Journal of Haematology|volume=156|issue=3|pages=358–365|doi=10.1111/j.1365-2141.2011.08955.x|issn=1365-2141|pmid=22128890}}</ref><ref name=":4">Borowitz MJ, et al., (2016).T-lymphoblastic leukemia/lymphoma, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4thedition.Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p176-178.</ref>. Some patients who develop an anterior mediastinal mass can lead to superior vena cava syndrome. | ||
| Line 100: | Line 100: | ||
!Notes | !Notes | ||
|- | |- | ||
| − | |EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC) | + | |<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)||<span class="blue-text">EXAMPLE:</span> 3'ABL1 / 5'BCR||<span class="blue-text">EXAMPLE:</span> der(22)||<span class="blue-text">EXAMPLE:</span> 20% (COSMIC) |
| − | EXAMPLE 30% (add reference) | + | <span class="blue-text">EXAMPLE:</span> 30% (add reference) |
|Yes | |Yes | ||
|No | |No | ||
|Yes | |Yes | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
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). | 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). | ||
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| − | <blockquote class='blockedit'>{{Box-round|title= | + | <blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|The content below was from the previous version of the page. Please incorporate above.}} |
''MEF2C'' (5q14) rearrangement or rearrangement involving ''MEF2C''-related cofactors have been reported in about 50% of ETP-ALL cases<ref>Homminga I, Pieters R, Langerak A, de Rooi J, Stubbs A, Verstegen M, et al. MEF2C as Novel Oncogene for Early T-Cell Precursor (ETP) Leukemia. ''Blood'' (2010) 116:9–9. doi: 10.1182/blood.V116.21.9.9</ref>, which have been validated in an independent ETP-ALL patient cohort<ref>Meijer M, Cordo V, Hagelaar R, Smits W, Meijerink J. Manipulating MEF2C: Discovering Novel Drugs to Target ETP-ALL. ''Blood'' (2021) 138 (Supplement 1): 3325. doi.org/10.1182/blood-2021-150176.</ref>. Ectopic MEF2C expression due to rearrangement has been demonstrated as an oncogenic driver of ETP-ALL by upregulating ''LMO2'' and ''LYL1,'' which lead to differentiation block of early thymocytes. | ''MEF2C'' (5q14) rearrangement or rearrangement involving ''MEF2C''-related cofactors have been reported in about 50% of ETP-ALL cases<ref>Homminga I, Pieters R, Langerak A, de Rooi J, Stubbs A, Verstegen M, et al. MEF2C as Novel Oncogene for Early T-Cell Precursor (ETP) Leukemia. ''Blood'' (2010) 116:9–9. doi: 10.1182/blood.V116.21.9.9</ref>, which have been validated in an independent ETP-ALL patient cohort<ref>Meijer M, Cordo V, Hagelaar R, Smits W, Meijerink J. Manipulating MEF2C: Discovering Novel Drugs to Target ETP-ALL. ''Blood'' (2021) 138 (Supplement 1): 3325. doi.org/10.1182/blood-2021-150176.</ref>. Ectopic MEF2C expression due to rearrangement has been demonstrated as an oncogenic driver of ETP-ALL by upregulating ''LMO2'' and ''LYL1,'' which lead to differentiation block of early thymocytes. | ||
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==Individual Region Genomic Gain / Loss / LOH== | ==Individual Region Genomic Gain / Loss / LOH== | ||
| − | Put your text here and fill in the table <span style="color:#0070C0">(''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.'') </span> | + | Put your text here and fill in the table <span style="color:#0070C0">(''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.'') </span> |
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
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!Notes | !Notes | ||
|- | |- | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
7 | 7 | ||
| − | |EXAMPLE Loss | + | |<span class="blue-text">EXAMPLE:</span> Loss |
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
chr7:1- 159,335,973 [hg38] | chr7:1- 159,335,973 [hg38] | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
chr7 | chr7 | ||
| Line 144: | Line 144: | ||
|Yes | |Yes | ||
|No | |No | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference). | Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference). | ||
|- | |- | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
8 | 8 | ||
| − | |EXAMPLE Gain | + | |<span class="blue-text">EXAMPLE:</span> Gain |
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
chr8:1-145,138,636 [hg38] | chr8:1-145,138,636 [hg38] | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
chr8 | chr8 | ||
| Line 161: | Line 161: | ||
|No | |No | ||
|No | |No | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
Common recurrent secondary finding for t(8;21) (add reference). | Common recurrent secondary finding for t(8;21) (add reference). | ||
|} | |} | ||
| − | <blockquote class='blockedit'>{{Box-round|title= | + | <blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|The content below was from the previous version of the page. Please incorporate above.}} |
Currently there is no specific copy number alterations/LOH that is associated with ETP-ALL. | Currently there is no specific copy number alterations/LOH that is associated with ETP-ALL. | ||
| Line 172: | Line 172: | ||
==Characteristic Chromosomal Patterns== | ==Characteristic Chromosomal Patterns== | ||
| − | Put your text here <span style="color:#0070C0">(''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'')</span> | + | Put your text here <span style="color:#0070C0">(''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.'')</span> |
{| class="wikitable sortable" | {| class="wikitable sortable" | ||
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!Notes | !Notes | ||
|- | |- | ||
| − | |EXAMPLE | + | |<span class="blue-text">EXAMPLE:</span> |
Co-deletion of 1p and 18q | Co-deletion of 1p and 18q | ||
| Line 188: | Line 188: | ||
|No | |No | ||
|No | |No | ||
| − | |EXAMPLE: | + | |<span class="blue-text">EXAMPLE:</span> |
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). | See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). | ||
|} | |} | ||
| − | <blockquote class='blockedit'>{{Box-round|title= | + | <blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|The content below was from the previous version of the page. Please incorporate above.}} |
Currently there is no specific chromosomal alteration that is characteristic for ETP-ALL. | Currently there is no specific chromosomal alteration that is characteristic for ETP-ALL. | ||
Revision as of 11:34, 1 September 2024
Haematolymphoid Tumours (WHO Classification, 5th ed.)
 | This page is under construction |
editHAEM5 Conversion NotesThis page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Early T-Cell Precursor Lymphoblastic Leukemia.
(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)*
Fei Yang, MD, FACMG, Kaiser Permanente Northwest
Cancer Category / Type
T-Lymphoblastic Leukemia (T-ALL)
Cancer Sub-Classification / Subtype
Early T-Cell Precursor Lymphoblastic Leukemia (ETP-ALL)
Definition / Description of Disease
Early T-Cell Precursor Lymphoblastic Leukemia (ETP-ALL) is a subtype of T-Lymphoblastic Leukemia (T-ALL) and is suggested to derive from thymic cells at the early T-cell precursor (ETP) differentiation stage[1]. The normal counterpart is the ETP cells that are the earliest thymic progenitors immigrated from the bone marrow to the thymus, with retention of a certain level of multilineage pluripotency rather than common lymphoid progenitors [2]. The ETP-ALL subtype has characteristic immunophenotypic and genomic profile compared with other subtypes of T-ALL. Under the 2016 version World Health Organization (WHO) classification[3], ETP-ALL is defined based on the immunophenotype of the leukemic cells:
- positive for intracytoplasmic CD3 and CD7, and positive (≥25% of blasts population) for at least one stem cell/myeloid marker (CD117, CD34, HLA-DR, CD13, CD33, CD11b, or CD65)
- negative to dim positive for CD5 (<75% positive)
- negative for CD1a, CD8, and MPO
However, the aforementioned immunophenotypic criteria have been reported not be able to identify all ETP-ALL cases as detected by gene expression profiling, and "negativity for CD4" has been proposed to be added to the criteria [4].
Synonyms / Terminology
Early thymic precursor (ETP) acute lymphoblastic leukemia (ALL)[5]
Epidemiology / Prevalence
Early T-Cell Precursor Lymphoblastic Leukemia (ETP-ALL) is uncommon, reported in about 5-17% of pediatric acute lymphoblastic leukemia (ALL) and 5-10% of adult ALL cases, respectively[2][6][7].
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 | EXAMPLE: Asymptomatic (incidental finding on complete blood counts)
EXAMPLE: B-symptoms (weight loss, fever, night sweats) EXAMPLE: Fatigue EXAMPLE: Lymphadenopathy (uncommon) |
| Laboratory Findings | EXAMPLE: Cytopenias
EXAMPLE: Lymphocytosis (low level) |
editHAEM5 Conversion NotesThe content below was from the previous version of the page. Please incorporate above.The clinical features of ETP-ALL are similar to that of other subtypes of T-ALL, including a high leukocyte count, anterior mediastinal mass or other tissue mass, lymphadenopathy, hepatosplenomegaly[8][7]. Some patients who develop an anterior mediastinal mass can lead to superior vena cava syndrome.
Sites of Involvement
Similar to non-ETP T-ALL, the sites of involvement include bone marrow, lymph node, extra nodal and anterior mediastinal mass (thymus)[8][7].
Morphologic Features
Currently there is no specific morphologic feature reported for ETP-ALL.
Immunophenotype
| Finding | Marker |
|---|---|
| Positive (universal) | intracytoplasmic CD3, CD7, and at least one stem cell or myeloid antigen (CD34, HLA-DR, CD13, CD33, CD117, CD11b, CD65)[3][9][6] |
| Positive (subset) | dim expression of CD5 (<75% positive)[3][6], CD2[3] |
| Negative (universal) | CD1a, CD8[3][6] |
| Negative (subset) | CD5[3][6] |
Chromosomal Rearrangements (Gene Fusions)
Put your text here and fill in the 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 |
|---|---|---|---|---|---|---|---|
| EXAMPLE: t(9;22)(q34;q11.2) | EXAMPLE: 3'ABL1 / 5'BCR | EXAMPLE: der(22) | EXAMPLE: 20% (COSMIC)
EXAMPLE: 30% (add reference) |
Yes | 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). |
editHAEM5 Conversion NotesThe content below was from the previous version of the page. Please incorporate above.MEF2C (5q14) rearrangement or rearrangement involving MEF2C-related cofactors have been reported in about 50% of ETP-ALL cases[10], which have been validated in an independent ETP-ALL patient cohort[11]. Ectopic MEF2C expression due to rearrangement has been demonstrated as an oncogenic driver of ETP-ALL by upregulating LMO2 and LYL1, which lead to differentiation block of early thymocytes.
STIL-TAL1 fusion was only found in 3/23 ETP-ALL cases but not in 7 T-lymphoid/myeloid mixed phenotype acute leukemia (T/M-MPAL) cases in a study by Noronha et al [12], which could potentially help in distinguish these two disease entities. Further studies are warranted to confirm this finding.
Other chromosomal rearrangements involving KMT2A have been observed in ETP-ALL [12].
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 |
|---|---|---|---|---|---|---|---|
| EXAMPLE:
7 |
EXAMPLE: Loss | EXAMPLE:
chr7:1- 159,335,973 [hg38] |
EXAMPLE:
chr7 |
Yes | Yes | No | EXAMPLE:
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference). |
| EXAMPLE:
8 |
EXAMPLE: Gain | EXAMPLE:
chr8:1-145,138,636 [hg38] |
EXAMPLE:
chr8 |
No | No | No | EXAMPLE:
Common recurrent secondary finding for t(8;21) (add reference). |
editHAEM5 Conversion NotesThe content below was from the previous version of the page. Please incorporate above.Currently there is no specific copy number alterations/LOH that is associated with ETP-ALL.
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 |
|---|---|---|---|---|
| EXAMPLE:
Co-deletion of 1p and 18q |
Yes | No | No | EXAMPLE:
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). |
editHAEM5 Conversion NotesThe content below was from the previous version of the page. Please incorporate above.Currently there is no specific chromosomal alteration that is characteristic for ETP-ALL.
Gene Mutations (SNV / INDEL)
Genes encoding transcription factors for development and differentiation (ETV6, GATA3, HOXA, LMO2, RUNX1, WT1), kinase signaling (FLT3, JAK1, JAK3, IL7R, KRAS, NRAS), and epigenetic modifiers (DNMT3A, EED, EZH2, PHF6, SUZ12) are commonly mutated in ETP-ALL [6]. More typical T-ALL mutations, such as NOTCH1 mutations and CDKN1/2 mutations are less frequent in ETP-ALL [2].
| 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 |
|---|---|---|---|---|---|---|---|---|
| IL7R; Variable activating mutations | Oncogene | 33 - 42% in adult ETP-ALL [13][14] | core componenets of the PRC2: EZH2, SUZ12, and EED | associated with slow response to chemotherapy [13] | Ruxolitinib is evaluated in pre-clinical and clinical studies [15][16][6] | |||
| Components of PRC2: EZH2, SUZ12, EED; variable LOF mutations | TSG | 48% of pediatric ETP-ALL [14] | BET inhibitors are evaluated in the pre-clinical studies [17] | |||||
| FLT3; Activating mutations including ITD and TKD | Oncogene | 35% of adult ETP-ALL [18] | FLT3 inhibitors are evaluated in the pre-clinical studies [18] |
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
GATA3 encodes a transcription factor that is required for the development of T lymphocytes at multiple late differentiation steps [19]. Silencing of GATA3 via hypermethylation has been observed in 33% of adult ETP-ALL in a study of 70 adult ETP-ALL patients [20].
Genes and Main Pathways Involved
| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| EZH2, SUZ12, and EED; Inactivating mutations | Epigenetic regulation/Histone modification | cell maturation arrest |
| IL7R; Activating mutations | JAK/STAT signaling pathway | cell differentiation block |
Genetic Diagnostic Testing Methods
Clinical, morphological, and immunophenotypic findings are generally sufficient for diagnosis. ETP-ALL has distinct gene expression profile, however, this approach is not feasible in the current setting of routine diagnostic laboratories.
Familial Forms
Unknown
Additional Information
The prognosis of this disease entity was initially considered poor compared to other subtypes of T-ALL based on few small studies [1][8][21]. However, more recent studies with larger patient cohorts suggested that the overall outcome with appropriate therapy appeared to not differ significantly from other subtypes [22][23].
Links
N/A
References
- ↑ 1.0 1.1 Coustan-Smith, Elaine; et al. (2009-02). "Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia". The Lancet. Oncology. 10 (2): 147–156. doi:10.1016/S1470-2045(08)70314-0. ISSN 1474-5488. PMC 2840241. PMID 19147408. Check date values in:
|date=(help) - ↑ 2.0 2.1 2.2 Jain, Nitin; et al. (2016-04-14). "Early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) in adolescents and adults: a high-risk subtype". Blood. 127 (15): 1863–1869. doi:10.1182/blood-2015-08-661702. ISSN 1528-0020. PMC 4915808. PMID 26747249.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Arber, Daniel A.; et al. (2016-05-19). "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia". Blood. 127 (20): 2391–2405. doi:10.1182/blood-2016-03-643544. ISSN 1528-0020. PMID 27069254.
- ↑ Zuurbier, Linda; et al. (2014-01). "Immature MEF2C-dysregulated T-cell leukemia patients have an early T-cell precursor acute lymphoblastic leukemia gene signature and typically have non-rearranged T-cell receptors". Haematologica. 99 (1): 94–102. doi:10.3324/haematol.2013.090233. ISSN 1592-8721. PMC 4007923. PMID 23975177. Check date values in:
|date=(help) - ↑ Bond, Jonathan; et al. (2017-08-10). "Early Response-Based Therapy Stratification Improves Survival in Adult Early Thymic Precursor Acute Lymphoblastic Leukemia: A Group for Research on Adult Acute Lymphoblastic Leukemia Study". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 35 (23): 2683–2691. doi:10.1200/JCO.2016.71.8585. ISSN 1527-7755. PMID 28605290.
- ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 Sin, Chun-Fung; et al. (2021). "Early T-Cell Precursor Acute Lymphoblastic Leukemia: Diagnosis, Updates in Molecular Pathogenesis, Management, and Novel Therapies". Frontiers in Oncology. 11: 750789. doi:10.3389/fonc.2021.750789. ISSN 2234-943X. PMC 8666570 Check
|pmc=value (help). PMID 34912707 Check|pmid=value (help). - ↑ 7.0 7.1 7.2 Borowitz MJ, et al., (2016).T-lymphoblastic leukemia/lymphoma, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4thedition.Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p176-178.
- ↑ 8.0 8.1 8.2 Inukai, Takeshi; et al. (2012-02). "Clinical significance of early T-cell precursor acute lymphoblastic leukaemia: results of the Tokyo Children's Cancer Study Group Study L99-15". British Journal of Haematology. 156 (3): 358–365. doi:10.1111/j.1365-2141.2011.08955.x. ISSN 1365-2141. PMID 22128890. Check date values in:
|date=(help) - ↑ Raetz, Elizabeth A.; et al. (2016-12-02). "T-cell acute lymphoblastic leukemia". Hematology. 2016 (1): 580–588. doi:10.1182/asheducation-2016.1.580. ISSN 1520-4391. PMC 6142501. PMID 27913532.CS1 maint: PMC format (link)
- ↑ Homminga I, Pieters R, Langerak A, de Rooi J, Stubbs A, Verstegen M, et al. MEF2C as Novel Oncogene for Early T-Cell Precursor (ETP) Leukemia. Blood (2010) 116:9–9. doi: 10.1182/blood.V116.21.9.9
- ↑ Meijer M, Cordo V, Hagelaar R, Smits W, Meijerink J. Manipulating MEF2C: Discovering Novel Drugs to Target ETP-ALL. Blood (2021) 138 (Supplement 1): 3325. doi.org/10.1182/blood-2021-150176.
- ↑ 12.0 12.1 Noronha, Elda Pereira; et al. (2019). "T-lymphoid/myeloid mixed phenotype acute leukemia and early T-cell precursor lymphoblastic leukemia similarities with NOTCH1 mutation as a good prognostic factor". Cancer Management and Research. 11: 3933–3943. doi:10.2147/CMAR.S196574. ISSN 1179-1322. PMC 6504706. PMID 31118806.
- ↑ 13.0 13.1 Kim, Rathana; et al. (2020-07). "Adult T-cell acute lymphoblastic leukemias with IL7R pathway mutations are slow-responders who do not benefit from allogeneic stem-cell transplantation". Leukemia. 34 (7): 1730–1740. doi:10.1038/s41375-019-0685-4. ISSN 1476-5551. PMID 31992840. Check date values in:
|date=(help) - ↑ 14.0 14.1 Zhang, Jinghui; et al. (2012-01-11). "The genetic basis of early T-cell precursor acute lymphoblastic leukaemia". Nature. 481 (7380): 157–163. doi:10.1038/nature10725. ISSN 1476-4687. PMC 3267575. PMID 22237106.
- ↑ Delgado-Martin, C.; et al. (2017-12). "JAK/STAT pathway inhibition overcomes IL7-induced glucocorticoid resistance in a subset of human T-cell acute lymphoblastic leukemias". Leukemia. 31 (12): 2568–2576. doi:10.1038/leu.2017.136. ISSN 1476-5551. PMC 5729333. PMID 28484265. Check date values in:
|date=(help) - ↑ Maude, Shannon L.; et al. (2015-03-12). "Efficacy of JAK/STAT pathway inhibition in murine xenograft models of early T-cell precursor (ETP) acute lymphoblastic leukemia". Blood. 125 (11): 1759–1767. doi:10.1182/blood-2014-06-580480. ISSN 1528-0020. PMC 4357583. PMID 25645356.
- ↑ Andrieu, Guillaume P.; et al. (2021-11-11). "PRC2 loss of function confers a targetable vulnerability to BET proteins in T-ALL". Blood. 138 (19): 1855–1869. doi:10.1182/blood.2020010081. ISSN 1528-0020. PMID 34125178 Check
|pmid=value (help). - ↑ 18.0 18.1 Neumann, Martin; et al. (2013). "FLT3 mutations in early T-cell precursor ALL characterize a stem cell like leukemia and imply the clinical use of tyrosine kinase inhibitors". PloS One. 8 (1): e53190. doi:10.1371/journal.pone.0053190. ISSN 1932-6203. PMC 3554732. PMID 23359050.
- ↑ Hosoya, Tomonori; et al. (2009-12-21). "GATA-3 is required for early T lineage progenitor development". The Journal of Experimental Medicine. 206 (13): 2987–3000. doi:10.1084/jem.20090934. ISSN 1540-9538. PMC 2806453. PMID 19934022.
- ↑ Fransecky, L.; et al. (2016-09-22). "Silencing of GATA3 defines a novel stem cell-like subgroup of ETP-ALL". Journal of Hematology & Oncology. 9 (1): 95. doi:10.1186/s13045-016-0324-8. ISSN 1756-8722. PMC 5034449. PMID 27658391.
- ↑ Ma, Meilin; et al. (2012-12). "Early T-cell precursor leukemia: a subtype of high risk childhood acute lymphoblastic leukemia". Frontiers of Medicine. 6 (4): 416–420. doi:10.1007/s11684-012-0224-4. ISSN 2095-0225. PMID 23065427. Check date values in:
|date=(help) - ↑ Patrick, Katharine; et al. (2014-08). "Outcome for children and young people with Early T-cell precursor acute lymphoblastic leukaemia treated on a contemporary protocol, UKALL 2003". British Journal of Haematology. 166 (3): 421–424. doi:10.1111/bjh.12882. ISSN 1365-2141. PMID 24708207. Check date values in:
|date=(help) - ↑ Wood, Brent L.; et al. (2014-12-06). "T-Lymphoblastic Leukemia (T-ALL) Shows Excellent Outcome, Lack of Significance of the Early Thymic Precursor (ETP) Immunophenotype, and Validation of the Prognostic Value of End-Induction Minimal Residual Disease (MRD) in Children's Oncology Group (COG) Study AALL0434". Blood. 124 (21): 1–1. doi:10.1182/blood.V124.21.1.1. ISSN 0006-4971.
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