Philadelphia chromosome-like acute lymphoblastic leukemia

Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL), also referred to as - -like ALL, is a high-risk subset with a gene expression profile that shares significant overlap with that of Ph-positive (Ph ) ALL and is suggestive of activated kinase signaling. Although Ph ALL is defined b...

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Vydané v:Blood Ročník 130; číslo 19; s. 2064
Hlavní autori: Tasian, Sarah K, Loh, Mignon L, Hunger, Stephen P
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 09.11.2017
Predmet:
Animals
Fusion Proteins, bcr-abl - genetics
Fusion Proteins, bcr-abl - metabolism
Humans
Philadelphia Chromosome
Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism
Signal Transduction - genetics
Translocation, Genetic
ISSN:1528-0020, 1528-0020
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Popis
Shrnutí:Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL), also referred to as - -like ALL, is a high-risk subset with a gene expression profile that shares significant overlap with that of Ph-positive (Ph ) ALL and is suggestive of activated kinase signaling. Although Ph ALL is defined by - fusion, Ph-like ALL cases contain a variety of genomic alterations that activate kinase and cytokine receptor signaling. These alterations can be grouped into major subclasses that include ABL-class fusions involving ABL1, ABL2, CSF1R, and PDGFRB that phenocopy BCR-ABL1 and alterations of CRLF2, JAK2, and EPOR that activate JAK/STAT signaling. Additional genomic alterations in Ph-like ALL activate other kinases, including BLNK, DGKH, FGFR1, IL2RB, LYN, NTRK3, PDGFRA, PTK2B, TYK2, and the RAS signaling pathway. Recent studies have helped to define the genomic landscape of Ph-like ALL and how it varies across the age spectrum, associated clinical features and outcomes, and genetic risk factors. Preclinical studies and anecdotal reports show that targeted inhibitors of relevant signaling pathways are active in specific Ph-like ALL subsets, and precision medicine trials have been initiated for this high-risk ALL subset.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
ObjectType-Review-3
content type line 23
ISSN:1528-0020
1528-0020
DOI:10.1182/blood-2017-06-743252