Matches in SemOpenAlex for { <https://semopenalex.org/work/W2178468712> ?p ?o ?g. }
- W2178468712 endingPage "1343" @default.
- W2178468712 startingPage "1328" @default.
- W2178468712 abstract "Abstract Earlier in the past century, infections were regarded as the most likely cause of childhood B-cell precursor acute lymphoblastic leukemia (pB-ALL). However, there is a lack of relevant biologic evidence supporting this hypothesis. We present in vivo genetic evidence mechanistically connecting inherited susceptibility to pB-ALL and postnatal infections by showing that pB-ALL was initiated in Pax5 heterozygous mice only when they were exposed to common pathogens. Strikingly, these murine pB-ALLs closely resemble the human disease. Tumor exome sequencing revealed activating somatic, nonsynonymous mutations of Jak3 as a second hit. Transplantation experiments and deep sequencing suggest that inactivating mutations in Pax5 promote leukemogenesis by creating an aberrant progenitor compartment that is susceptible to malignant transformation through accumulation of secondary Jak3 mutations. Thus, treatment of Pax5+/− leukemic cells with specific JAK1/3 inhibitors resulted in increased apoptosis. These results uncover the causal role of infection in pB-ALL development. Significance: These results demonstrate that delayed infection exposure is a causal factor in pB-ALL. Therefore, these findings have critical implications for the understanding of the pathogenesis of leukemia and for the development of novel therapies for this disease. Cancer Discov; 5(12); 1328–43. ©2015 AACR. See related commentary by Greaves and Müschen, p. 1244. This article is highlighted in the In This Issue feature, p. 1225" @default.
- W2178468712 created "2016-06-24" @default.
- W2178468712 creator A5002071945 @default.
- W2178468712 creator A5017625141 @default.
- W2178468712 creator A5021529576 @default.
- W2178468712 creator A5027098748 @default.
- W2178468712 creator A5027206365 @default.
- W2178468712 creator A5032050812 @default.
- W2178468712 creator A5033002324 @default.
- W2178468712 creator A5033634773 @default.
- W2178468712 creator A5040964471 @default.
- W2178468712 creator A5044395832 @default.
- W2178468712 creator A5048431121 @default.
- W2178468712 creator A5051665031 @default.
- W2178468712 creator A5058587574 @default.
- W2178468712 creator A5062364819 @default.
- W2178468712 creator A5062623358 @default.
- W2178468712 creator A5065657518 @default.
- W2178468712 creator A5068063330 @default.
- W2178468712 creator A5068819185 @default.
- W2178468712 creator A5075974674 @default.
- W2178468712 creator A5077566992 @default.
- W2178468712 creator A5086294439 @default.
- W2178468712 creator A5088409474 @default.
- W2178468712 creator A5090598948 @default.
- W2178468712 date "2015-12-01" @default.
- W2178468712 modified "2023-10-11" @default.
- W2178468712 title "Infection Exposure Is a Causal Factor in B-cell Precursor Acute Lymphoblastic Leukemia as a Result of <i>Pax5</i>-Inherited Susceptibility" @default.
- W2178468712 cites W1649547160 @default.
- W2178468712 cites W1948212455 @default.
- W2178468712 cites W1964110508 @default.
- W2178468712 cites W1966384388 @default.
- W2178468712 cites W1969041059 @default.
- W2178468712 cites W1972682349 @default.
- W2178468712 cites W1973234860 @default.
- W2178468712 cites W1978326072 @default.
- W2178468712 cites W1984065010 @default.
- W2178468712 cites W1986263057 @default.
- W2178468712 cites W1993648538 @default.
- W2178468712 cites W1994222584 @default.
- W2178468712 cites W2009942084 @default.
- W2178468712 cites W2020541351 @default.
- W2178468712 cites W2021877756 @default.
- W2178468712 cites W2028601867 @default.
- W2178468712 cites W2035502959 @default.
- W2178468712 cites W2038588592 @default.
- W2178468712 cites W2040329520 @default.
- W2178468712 cites W2056265881 @default.
- W2178468712 cites W2081474521 @default.
- W2178468712 cites W2089478119 @default.
- W2178468712 cites W2102140136 @default.
- W2178468712 cites W2109972881 @default.
- W2178468712 cites W2120865735 @default.
- W2178468712 cites W2123561809 @default.
- W2178468712 cites W2130410032 @default.
- W2178468712 cites W2130807641 @default.
- W2178468712 cites W2132109848 @default.
- W2178468712 cites W2133118937 @default.
- W2178468712 cites W2134146607 @default.
- W2178468712 cites W2138601221 @default.
- W2178468712 cites W2140946267 @default.
- W2178468712 cites W2143585943 @default.
- W2178468712 cites W2151645052 @default.
- W2178468712 cites W2152733627 @default.
- W2178468712 cites W2155943701 @default.
- W2178468712 cites W2157838058 @default.
- W2178468712 cites W2160697532 @default.
- W2178468712 cites W2170222864 @default.
- W2178468712 cites W2170989872 @default.
- W2178468712 cites W2174323117 @default.
- W2178468712 cites W2326949152 @default.
- W2178468712 cites W4294107304 @default.
- W2178468712 doi "https://doi.org/10.1158/2159-8290.cd-15-0892" @default.
- W2178468712 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26408659" @default.
- W2178468712 hasPublicationYear "2015" @default.
- W2178468712 type Work @default.
- W2178468712 sameAs 2178468712 @default.
- W2178468712 citedByCount "107" @default.
- W2178468712 countsByYear W21784687122015 @default.
- W2178468712 countsByYear W21784687122016 @default.
- W2178468712 countsByYear W21784687122017 @default.
- W2178468712 countsByYear W21784687122018 @default.
- W2178468712 countsByYear W21784687122019 @default.
- W2178468712 countsByYear W21784687122020 @default.
- W2178468712 countsByYear W21784687122021 @default.
- W2178468712 countsByYear W21784687122022 @default.
- W2178468712 countsByYear W21784687122023 @default.
- W2178468712 crossrefType "journal-article" @default.
- W2178468712 hasAuthorship W2178468712A5002071945 @default.
- W2178468712 hasAuthorship W2178468712A5017625141 @default.
- W2178468712 hasAuthorship W2178468712A5021529576 @default.
- W2178468712 hasAuthorship W2178468712A5027098748 @default.
- W2178468712 hasAuthorship W2178468712A5027206365 @default.
- W2178468712 hasAuthorship W2178468712A5032050812 @default.
- W2178468712 hasAuthorship W2178468712A5033002324 @default.
- W2178468712 hasAuthorship W2178468712A5033634773 @default.
- W2178468712 hasAuthorship W2178468712A5040964471 @default.
- W2178468712 hasAuthorship W2178468712A5044395832 @default.