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| ==Primary Author(s)*== | | ==Primary Author(s)*== |
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| Xinxiu Xu, Vanderbilt University Medical Center | | Xinxiu Xu PhD, PharmB, Vanderbilt University Medical Center |
| ==WHO Classification of Disease== | | ==WHO Classification of Disease== |
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| |WHO Essential Criteria (Genetics)* | | |WHO Essential Criteria (Genetics)* |
| | | | |a myeloid neoplasm with >20% blasts expressing a myeloid immunophenotype in the bone marrow and/or peripheral blood; detection of ''BCR::ABL1'' at initial diagnosis; lack of features of CML before or at diagnosis or after therapy. |
| |- | | |- |
| |WHO Desirable Criteria (Genetics)* | | |WHO Desirable Criteria (Genetics)* |
| | | | |presence of t(9;22)(q34;q11.2) on conventional karyotyping; determination of the ''BCR::ABL1'' transcript subtype and establishment of a baseline level of ''BCR::ABL1'' transcript subtype and establishment of a baseline level of ''BCR::ABL1'' transcript for monitoring treatment response. |
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| |Other Classification | | |Other Classification |
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| |Acceptable | | |Acceptable |
| | | | |acute myeloid leukaemia with t(9;22)(q34;q11.2) |
| |- | | |- |
| |Not Recommended | | |Not Recommended |
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| !Clinical Relevance Details/Other Notes | | !Clinical Relevance Details/Other Notes |
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| |<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2) | | |''ABL1''||''BCR::ABL1''||The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||t(9;22)(q34;q11.2) |
| |<span class="blue-text">EXAMPLE:</span> Common (CML) | | |Common (CML) |
| |<span class="blue-text">EXAMPLE:</span> D, P, T | | |D, P, T |
| |<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN) | | |Yes (WHO, NCCN) |
| |<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). BCR::ABL1 is generally favorable in CML (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). BCR::ABL1 is generally favorable in CML (add reference). | |
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| |<span class="blue-text">EXAMPLE:</span> ''CIC''
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| |<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
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| |<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
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| |<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
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| |<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
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| |<span class="blue-text">EXAMPLE:</span> D
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| |<span class="blue-text">EXAMPLE:</span>
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| ''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
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| |<span class="blue-text">EXAMPLE:</span> ''ALK''
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| |<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
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| Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
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| |<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
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| |<span class="blue-text">EXAMPLE:</span> N/A
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| |<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
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| |<span class="blue-text">EXAMPLE:</span> T
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| |<span class="blue-text">EXAMPLE:</span>
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| Both balanced and unbalanced forms are observed by FISH (add references).
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| |<span class="blue-text">EXAMPLE:</span> ''ABL1''
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| |<span class="blue-text">EXAMPLE:</span> N/A
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| |<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
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| |<span class="blue-text">EXAMPLE:</span> N/A
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| |<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
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| |<span class="blue-text">EXAMPLE:</span> D, P, T
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| |} | | |} |
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