Hematological neoplasms associated with <i>ALK</i> fusion genes
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- Ohno Hitoshi
- Tenri Institute of Medical Research, Tenri Hospital
Bibliographic Information
- Other Title
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- <i>ALK</i>融合遺伝子を伴う造血器腫瘍
- Hematological neoplasms associated with ALK fusion genes
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Abstract
<p>The anaplastic lymphoma kinase gene (ALK) is located at chromosome 2p23 and encodes a transmembrane receptor tyrosine kinase. As a result of chromosomal translocation/inversion, the 3′ sequence of ALK fuses to the 5′ sequence of a partner gene, producing an oncogenic chimeric protein that activates downstream signal transduction pathways. ALK fusion genes are found in diverse tumor types of different lineages, including hematological neoplasms. ALK-positive (ALK+) anaplastic large cell lymphoma (ALCL) is a distinct subtype of peripheral T-cell lymphoma that is characterized by the expression of CD30 and ALK by immunohistochemistry (IHC). Approximately 70 to 80% of ALK+ ALCL cases have t(2;5)(p23;q35)/NPM1::ALK associated with the nuclear/cytoplasmic ALK IHC staining pattern. In the remaining cases, ALK fuses to various partner genes and ALK staining pattens vary with these partners. ALK+ large B-cell lymphoma (LBCL), accounting for <1% of all diffuse large B-cell lymphoma cases, is characterized by an immunoblast/plasmablast-like cytomorphology. ALK+ LBCL cases with t(2;17)(p23;q23)/CLTC::ALK show the cytoplasmic granular pattern of ALK IHC. Acute myeloid leukemia (AML) harboring inv(2)(p23q13)/RANBP2::ALK defines a small subset of AML characterized by monocytic differentiation and monosomy 7. Extramedullary plasmacytoma/multiple myeloma with the ALK fusion gene shares cytomorphological and immunophenotypic features with ALK+ LBCL. ALK+ histiocytosis is an emerging rare histiocytic entity and most cases carry KIF5B::ALK. The antibody-drug conjugate, brentuximab vedotin, which targets cell-surface CD30, is approved for the treatment of ALK+ ALCL as a single agent or in combination with other cytotoxic agents in both the front-line and relapsed/refractory (R/R) settings. R/R ALK+ hematological neoplasms respond well to first- to third-generation ALK tyrosine kinase inhibitors and an optimal treatment strategy including these novel agents is being tested. </p>
Journal
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- Tenri Medical Bulletin
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Tenri Medical Bulletin 26 (1), 32-53, 2023-12-25
Tenri Foundation, Tenri Institute of Medical Research
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Keywords
Details 詳細情報について
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- CRID
- 1390578141474123776
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- NII Book ID
- AA11350134
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- ISSN
- 21872244
- 13441817
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- NDL BIB ID
- 033262659
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
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- Abstract License Flag
- Disallowed