HAEM5:Adult T-cell leukaemia/lymphoma: Difference between revisions
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|Adult T-cell leukaemia/lymphoma, HTLV-1 associated | |Adult T-cell leukaemia/lymphoma, HTLV-1 associated | ||
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ATLL patients have high expression of polycomb repressive complex (PRC) 2 components like EZH2, its homolog EZH1 and H3K27 methylase causing accumulation of trimethylation of H3K27 and altering the expression of over half of the genes. The severity of the disease is linked to continued down regulation of genes<ref>{{Cite journal|last=Fujikawa|first=Dai|last2=Nakagawa|first2=Shota|last3=Hori|first3=Makoto|last4=Kurokawa|first4=Naoya|last5=Soejima|first5=Ai|last6=Nakano|first6=Kazumi|last7=Yamochi|first7=Tadanori|last8=Nakashima|first8=Makoto|last9=Kobayashi|first9=Seiichiro|date=2016-04-07|title=Polycomb-dependent epigenetic landscape in adult T-cell leukemia|url=https://pubmed.ncbi.nlm.nih.gov/26773042|journal=Blood|volume=127|issue=14|pages=1790–1802|doi=10.1182/blood-2015-08-662593|issn=1528-0020|pmid=26773042}}</ref>. | == Epigenomic Alterations == | ||
Epigenetic alterations also result in dysregulated TCR/NF-κB signaling in ATLL. DNA hypermethylation of CpG islands is detected in 1/3<sup>rd</sup> of all ATLL patients. As a result, genes involved in Cys2-His2 (C2H2) zinc finger genes and those encoding MHC class I molecules are silenced<ref name=":1" />. | |||
ATLL patients have high expression of polycomb repressive complex (PRC) 2 components like EZH2, its homolog EZH1 and H3K27 methylase causing accumulation of trimethylation of H3K27 and altering the expression of over half of the genes. The severity of the disease is linked to continued down regulation of genes<ref>{{Cite journal|last=Fujikawa|first=Dai|last2=Nakagawa|first2=Shota|last3=Hori|first3=Makoto|last4=Kurokawa|first4=Naoya|last5=Soejima|first5=Ai|last6=Nakano|first6=Kazumi|last7=Yamochi|first7=Tadanori|last8=Nakashima|first8=Makoto|last9=Kobayashi|first9=Seiichiro|date=2016-04-07|title=Polycomb-dependent epigenetic landscape in adult T-cell leukemia|url=https://pubmed.ncbi.nlm.nih.gov/26773042|journal=Blood|volume=127|issue=14|pages=1790–1802|doi=10.1182/blood-2015-08-662593|issn=1528-0020|pmid=26773042}}</ref>. | |||
==Genes and Main Pathways Involved== | == Genes and Main Pathways Involved == | ||
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" />. | 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" />. | ||
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Chemokine receptors including CCR4 and CCR7 are responsible for the infiltration of neoplastic cells into other organs along with activation of PI3K/AKT signaling. | Chemokine receptors including CCR4 and CCR7 are responsible for the infiltration of neoplastic cells into other organs along with activation of PI3K/AKT signaling. | ||
The epigenetic mechanism is also exploited to alter gene expression and promote ATLL progression as explained above | The epigenetic mechanism is also exploited to alter gene expression and promote ATLL progression as explained above<center><center> | ||
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|<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling | |<span class="blue-text">EXAMPLE:</span> Histone modification, chromatin remodeling | ||
|<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program | |<span class="blue-text">EXAMPLE:</span> Abnormal gene expression program | ||
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==Genetic Diagnostic Testing | |||
== Genetic Diagnostic Testing Method == | |||
Initial diagnosis of ATLL should include a comprehensive physical exam with skin evaluation and CT scans of the chest, abdomen and pelvis. The laboratory evaluation should include: a complete blood count (CBC), metabolic panel (serum electrolyte levels, calcium, creatinine and blood urea nitrogen) and serum LDH levels. Testing methods including PCR, Flow Cytometry, ELISA, serology, and immunohistochemistry in addition to morphologic studies may be employed to diagnose ATLL<ref name=":4">NCCN Clinical Practice Guidelines in Oncology, T-Cell Lymphomas, Version 1.2021. Available at NCCN.org.</ref>. | Initial diagnosis of ATLL should include a comprehensive physical exam with skin evaluation and CT scans of the chest, abdomen and pelvis. The laboratory evaluation should include: a complete blood count (CBC), metabolic panel (serum electrolyte levels, calcium, creatinine and blood urea nitrogen) and serum LDH levels. Testing methods including PCR, Flow Cytometry, ELISA, serology, and immunohistochemistry in addition to morphologic studies may be employed to diagnose ATLL<ref name=":4">NCCN Clinical Practice Guidelines in Oncology, T-Cell Lymphomas, Version 1.2021. Available at NCCN.org.</ref>. | ||
==Familial Forms== | == Familial Forms == | ||
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== Additional Information == | |||
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== | == References == | ||
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