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
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Abstract 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.
AbstractList Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL), also referred to as BCR-ABL1-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 BCR-ABL1 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.Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL), also referred to as BCR-ABL1-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 BCR-ABL1 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.
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.
Author Tasian, Sarah K
Hunger, Stephen P
Loh, Mignon L
Author_xml – sequence: 1
  givenname: Sarah K
  orcidid: 0000-0003-1327-1662
  surname: Tasian
  fullname: Tasian, Sarah K
  organization: Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and
– sequence: 2
  givenname: Mignon L
  orcidid: 0000-0003-4099-4700
  surname: Loh
  fullname: Loh, Mignon L
  organization: Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA
– sequence: 3
  givenname: Stephen P
  orcidid: 0000-0002-5492-3957
  surname: Hunger
  fullname: Hunger, Stephen P
  organization: Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28972016$$D View this record in MEDLINE/PubMed
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Snippet Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL), also referred to as - -like ALL, is a high-risk subset with a gene expression profile...
Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL), also referred to as BCR-ABL1-like ALL, is a high-risk subset with a gene expression...
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SubjectTerms 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
Title Philadelphia chromosome-like acute lymphoblastic leukemia
URI https://www.ncbi.nlm.nih.gov/pubmed/28972016
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