HAEM5:Adult T-cell leukaemia/lymphoma: Difference between revisions

{{DISPLAYTITLE:Adult T-cell leukaemia/lymphoma}}

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==Primary Author(s)*==

==Clinical Features==

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|'''Signs and Symptoms'''

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|'''Laboratory Findings'''

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ATLL is classified into four clinical subtypes: Acute, Lymphoma, Chronic and Smoldering<ref name=":3">{{Cite journal|last=Shimoyama|first=M.|date=1991-11|title=Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the Lymphoma Study Group (1984-87)|url=https://pubmed.ncbi.nlm.nih.gov/1751370|journal=British Journal of Haematology|volume=79|issue=3|pages=428–437|doi=10.1111/j.1365-2141.1991.tb08051.x|issn=0007-1048|pmid=1751370}}</ref>.  

!Notes

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|Yes

|No

|Yes

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).

Tandem duplications of  2q33.2 segments cause formation of CTLA4-CD28 and ICOS-CD28 fusion products that render prolonged co-stimulatory signals<ref name=":1">{{Cite journal|last=Kataoka|first=Keisuke|last2=Nagata|first2=Yasunobu|last3=Kitanaka|first3=Akira|last4=Shiraishi|first4=Yuichi|last5=Shimamura|first5=Teppei|last6=Yasunaga|first6=Jun-Ichirou|last7=Totoki|first7=Yasushi|last8=Chiba|first8=Kenichi|last9=Sato-Otsubo|first9=Aiko|date=2015-11|title=Integrated molecular analysis of adult T cell leukemia/lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26437031|journal=Nature Genetics|volume=47|issue=11|pages=1304–1315|doi=10.1038/ng.3415|issn=1546-1718|pmid=26437031}}</ref>.  

* Chromosomal Rearrangements (Gene Fusions)

* Individual Region Genomic Gain/Loss/LOH

==Individual Region Genomic Gain / Loss / LOH==

{| class="wikitable sortable"

!Notes

|-

7

chr7:1- 159,335,973 [hg38]

chr7

|Yes

|No

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).

|-

8

chr8:1-145,138,636 [hg38]

chr8

|No

|No

Common recurrent secondary finding for t(8;21) (add reference).

|}

ATLL with high number of chromosomal imbalances is associated with poor survival<ref>{{Cite journal|last=Itoyama|first=T.|last2=Chaganti|first2=R. S.|last3=Yamada|first3=Y.|last4=Tsukasaki|first4=K.|last5=Atogami|first5=S.|last6=Nakamura|first6=H.|last7=Tomonaga|first7=M.|last8=Ohshima|first8=K.|last9=Kikuchi|first9=M.|date=2001-06-01|title=Cytogenetic analysis and clinical significance in adult T-cell leukemia/lymphoma: a study of 50 cases from the human T-cell leukemia virus type-1 endemic area, Nagasaki|url=https://pubmed.ncbi.nlm.nih.gov/11369658|journal=Blood|volume=97|issue=11|pages=3612–3620|doi=10.1182/blood.v97.11.3612|issn=0006-4971|pmid=11369658}}</ref><ref>{{Cite journal|last=Tsukasaki|first=K.|last2=Krebs|first2=J.|last3=Nagai|first3=K.|last4=Tomonaga|first4=M.|last5=Koeffler|first5=H. P.|last6=Bartram|first6=C. R.|last7=Jauch|first7=A.|date=2001-06-15|title=Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course|url=https://pubmed.ncbi.nlm.nih.gov/11389029|journal=Blood|volume=97|issue=12|pages=3875–3881|doi=10.1182/blood.v97.12.3875|issn=0006-4971|pmid=11389029}}</ref><ref>{{Cite journal|last=Oshiro|first=Aya|last2=Tagawa|first2=Hiroyuki|last3=Ohshima|first3=Koichi|last4=Karube|first4=Kennosuke|last5=Uike|first5=Naokuni|last6=Tashiro|first6=Yukie|last7=Utsunomiya|first7=Atae|last8=Masuda|first8=Masato|last9=Takasu|first9=Nobuyuki|date=2006-06-01|title=Identification of subtype-specific genomic alterations in aggressive adult T-cell leukemia/lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/16484591|journal=Blood|volume=107|issue=11|pages=4500–4507|doi=10.1182/blood-2005-09-3801|issn=0006-4971|pmid=16484591}}</ref><ref name=":2">{{Cite journal|last=Kataoka|first=Keisuke|last2=Iwanaga|first2=Masako|last3=Yasunaga|first3=Jun-Ichirou|last4=Nagata|first4=Yasunobu|last5=Kitanaka|first5=Akira|last6=Kameda|first6=Takuro|last7=Yoshimitsu|first7=Makoto|last8=Shiraishi|first8=Yuichi|last9=Sato-Otsubo|first9=Aiko|date=01 11, 2018|title=Prognostic relevance of integrated genetic profiling in adult T-cell leukemia/lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/29084771|journal=Blood|volume=131|issue=2|pages=215–225|doi=10.1182/blood-2017-01-761874|issn=1528-0020|pmc=5757690|pmid=29084771}}</ref>.  

==Characteristic Chromosomal Patterns==

{| class="wikitable sortable"

!Notes

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Co-deletion of 1p and 18q

|No

|No

See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

|}

Cytogenetic studies show that ATLL often has a complex abnormal karyotype without a single distinct abnormality. Observed recurrent abnormalities include trisomy for 3, 7 or 21 and monosomy for X as well as deletion of Y and abnormalities of chromosome 6 and 14. Chromosome 14 rearrangements involving TCRA and TCRD at 14q11 and TCL1 at 14q32 have been documented<ref>{{Cite journal|date=1987-11|title=Correlation of chromosome abnormalities with histologic and immunologic characteristics in non-Hodgkin's lymphoma and adult T cell leukemia-lymphoma. Fifth International Workshop on Chromosomes in Leukemia-Lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/2889485|journal=Blood|volume=70|issue=5|pages=1554–1564|issn=0006-4971|pmid=2889485}}</ref>. Frequent deletions in known fragile sites have been detected in over 500 patients<ref name=":1" />.  

==Gene Mutations (SNV / INDEL)==

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!Notes

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EGFR; Exon 20 mutations

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|

<br />

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Over 10% of ATLL cases harbor mostly gain of function mutations. ATLL harbors multiple recurrent mutations in genes involved in the TCR-NF-κB pathway, tumor suppressors, transcription factors involved in cell growth and proliferation, apoptosis, and immune surveillance<ref>{{Cite journal|last=Kogure|first=Yasunori|last2=Kataoka|first2=Keisuke|date=2017-09|title=Genetic alterations in adult T-cell leukemia/lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/28627735|journal=Cancer Science|volume=108|issue=9|pages=1719–1725|doi=10.1111/cas.13303|issn=1349-7006|pmc=5581529|pmid=28627735}}</ref><ref name=":2" /><ref>{{Cite journal|last=Kataoka|first=Keisuke|last2=Nagata|first2=Yasunobu|last3=Kitanaka|first3=Akira|last4=Shiraishi|first4=Yuichi|last5=Shimamura|first5=Teppei|last6=Yasunaga|first6=Jun-Ichirou|last7=Totoki|first7=Yasushi|last8=Chiba|first8=Kenichi|last9=Sato-Otsubo|first9=Aiko|date=2015-11|title=Integrated molecular analysis of adult T cell leukemia/lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26437031|journal=Nature Genetics|volume=47|issue=11|pages=1304–1315|doi=10.1038/ng.3415|issn=1546-1718|pmid=26437031}}</ref>.  

!Type!!Gene/Region/Other

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==Genes and Main Pathways Involved==

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!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome

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The most important genes involved in the development and progress of ATLL are the Tax and HBZ contributed by the HTLV-1 virus and genes listed in gene mutations table (above) from the host. The main pathways involved are TCR-NF-κB signaling by gain of function and amplifications in PLCG1, VAV1 and FYN, CD28, PRKCB, CARD11, IRF4 and RHOA; and loss of function mutations or deletions in CBLB, TRAF, TNFAIP3 and CSNK1A1<ref name=":1" />.

==Links==

==References==