Mutant JAK3 signaling is increased by loss of wild-type JAK3 or by acquisition of secondary JAK3 mutations in T-ALL

Publication Date:
2018-01-26
Publisher:
American Society of Hematology (ASH)
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
Medicine
Keywords:
Lymphoid Neoplasia, Brief Reports
Published by:
http://www.hematology.org/
_version_ 1836398763671814145
autor Degryse, S., Bornschein, S., de Bock, C. E., Leroy, E., Vanden Bempt, M., Demeyer, S., Jacobs, K., Geerdens, E., Gielen, O., Soulier, J., Harrison, C. J., Constantinescu, S. N., Cools, J.
beschreibung The Janus kinase 3 (JAK3) tyrosine kinase is mutated in 10% to 16% of T-cell acute lymphoblastic leukemia (T-ALL) cases. JAK3 mutants induce constitutive JAK/STAT signaling and cause leukemia when expressed in the bone marrow cells of mice. Surprisingly, we observed that one third of JAK3-mutant T-ALL cases harbor 2 JAK3 mutations, some of which are monoallelic and others that are biallelic. Our data suggest that wild-type JAK3 competes with mutant JAK3 (M511I) for binding to the common chain and thereby suppresses its oncogenic potential. We demonstrate that JAK3 (M511I) can increase its limited oncogenic potential through the acquisition of an additional mutation in the mutant JAK3 allele. These double JAK3 mutants show increased STAT5 activation and increased potential to transform primary mouse pro–T cells to interleukin-7–independent growth and were not affected by wild-type JAK3 expression. These data extend our insight into the oncogenic properties of JAK3 mutations and provide an explanation of why progression of JAK3-mutant T-ALL cases can be associated with the accumulation of additional JAK3 mutations.
citation_standardnr 6146206
datenlieferant ipn_articles
feed_id 310
feed_publisher American Society of Hematology (ASH)
feed_publisher_url http://www.hematology.org/
insertion_date 2018-01-26
journaleissn 1528-0020
journalissn 0006-4971
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Society of Hematology (ASH)
quelle Blood
relation http://www.bloodjournal.org/cgi/content/short/131/4/421?rss=1
schlagwort Lymphoid Neoplasia, Brief Reports
search_space articles
shingle_author_1 Degryse, S., Bornschein, S., de Bock, C. E., Leroy, E., Vanden Bempt, M., Demeyer, S., Jacobs, K., Geerdens, E., Gielen, O., Soulier, J., Harrison, C. J., Constantinescu, S. N., Cools, J.
shingle_author_2 Degryse, S., Bornschein, S., de Bock, C. E., Leroy, E., Vanden Bempt, M., Demeyer, S., Jacobs, K., Geerdens, E., Gielen, O., Soulier, J., Harrison, C. J., Constantinescu, S. N., Cools, J.
shingle_author_3 Degryse, S., Bornschein, S., de Bock, C. E., Leroy, E., Vanden Bempt, M., Demeyer, S., Jacobs, K., Geerdens, E., Gielen, O., Soulier, J., Harrison, C. J., Constantinescu, S. N., Cools, J.
shingle_author_4 Degryse, S., Bornschein, S., de Bock, C. E., Leroy, E., Vanden Bempt, M., Demeyer, S., Jacobs, K., Geerdens, E., Gielen, O., Soulier, J., Harrison, C. J., Constantinescu, S. N., Cools, J.
shingle_catch_all_1 Mutant JAK3 signaling is increased by loss of wild-type JAK3 or by acquisition of secondary JAK3 mutations in T-ALL
Lymphoid Neoplasia, Brief Reports
The Janus kinase 3 (JAK3) tyrosine kinase is mutated in 10% to 16% of T-cell acute lymphoblastic leukemia (T-ALL) cases. JAK3 mutants induce constitutive JAK/STAT signaling and cause leukemia when expressed in the bone marrow cells of mice. Surprisingly, we observed that one third of JAK3-mutant T-ALL cases harbor 2 JAK3 mutations, some of which are monoallelic and others that are biallelic. Our data suggest that wild-type JAK3 competes with mutant JAK3 (M511I) for binding to the common chain and thereby suppresses its oncogenic potential. We demonstrate that JAK3 (M511I) can increase its limited oncogenic potential through the acquisition of an additional mutation in the mutant JAK3 allele. These double JAK3 mutants show increased STAT5 activation and increased potential to transform primary mouse pro–T cells to interleukin-7–independent growth and were not affected by wild-type JAK3 expression. These data extend our insight into the oncogenic properties of JAK3 mutations and provide an explanation of why progression of JAK3-mutant T-ALL cases can be associated with the accumulation of additional JAK3 mutations.
Degryse, S., Bornschein, S., de Bock, C. E., Leroy, E., Vanden Bempt, M., Demeyer, S., Jacobs, K., Geerdens, E., Gielen, O., Soulier, J., Harrison, C. J., Constantinescu, S. N., Cools, J.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_2 Mutant JAK3 signaling is increased by loss of wild-type JAK3 or by acquisition of secondary JAK3 mutations in T-ALL
Lymphoid Neoplasia, Brief Reports
The Janus kinase 3 (JAK3) tyrosine kinase is mutated in 10% to 16% of T-cell acute lymphoblastic leukemia (T-ALL) cases. JAK3 mutants induce constitutive JAK/STAT signaling and cause leukemia when expressed in the bone marrow cells of mice. Surprisingly, we observed that one third of JAK3-mutant T-ALL cases harbor 2 JAK3 mutations, some of which are monoallelic and others that are biallelic. Our data suggest that wild-type JAK3 competes with mutant JAK3 (M511I) for binding to the common chain and thereby suppresses its oncogenic potential. We demonstrate that JAK3 (M511I) can increase its limited oncogenic potential through the acquisition of an additional mutation in the mutant JAK3 allele. These double JAK3 mutants show increased STAT5 activation and increased potential to transform primary mouse pro–T cells to interleukin-7–independent growth and were not affected by wild-type JAK3 expression. These data extend our insight into the oncogenic properties of JAK3 mutations and provide an explanation of why progression of JAK3-mutant T-ALL cases can be associated with the accumulation of additional JAK3 mutations.
Degryse, S., Bornschein, S., de Bock, C. E., Leroy, E., Vanden Bempt, M., Demeyer, S., Jacobs, K., Geerdens, E., Gielen, O., Soulier, J., Harrison, C. J., Constantinescu, S. N., Cools, J.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_3 Mutant JAK3 signaling is increased by loss of wild-type JAK3 or by acquisition of secondary JAK3 mutations in T-ALL
Lymphoid Neoplasia, Brief Reports
The Janus kinase 3 (JAK3) tyrosine kinase is mutated in 10% to 16% of T-cell acute lymphoblastic leukemia (T-ALL) cases. JAK3 mutants induce constitutive JAK/STAT signaling and cause leukemia when expressed in the bone marrow cells of mice. Surprisingly, we observed that one third of JAK3-mutant T-ALL cases harbor 2 JAK3 mutations, some of which are monoallelic and others that are biallelic. Our data suggest that wild-type JAK3 competes with mutant JAK3 (M511I) for binding to the common chain and thereby suppresses its oncogenic potential. We demonstrate that JAK3 (M511I) can increase its limited oncogenic potential through the acquisition of an additional mutation in the mutant JAK3 allele. These double JAK3 mutants show increased STAT5 activation and increased potential to transform primary mouse pro–T cells to interleukin-7–independent growth and were not affected by wild-type JAK3 expression. These data extend our insight into the oncogenic properties of JAK3 mutations and provide an explanation of why progression of JAK3-mutant T-ALL cases can be associated with the accumulation of additional JAK3 mutations.
Degryse, S., Bornschein, S., de Bock, C. E., Leroy, E., Vanden Bempt, M., Demeyer, S., Jacobs, K., Geerdens, E., Gielen, O., Soulier, J., Harrison, C. J., Constantinescu, S. N., Cools, J.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_catch_all_4 Mutant JAK3 signaling is increased by loss of wild-type JAK3 or by acquisition of secondary JAK3 mutations in T-ALL
Lymphoid Neoplasia, Brief Reports
The Janus kinase 3 (JAK3) tyrosine kinase is mutated in 10% to 16% of T-cell acute lymphoblastic leukemia (T-ALL) cases. JAK3 mutants induce constitutive JAK/STAT signaling and cause leukemia when expressed in the bone marrow cells of mice. Surprisingly, we observed that one third of JAK3-mutant T-ALL cases harbor 2 JAK3 mutations, some of which are monoallelic and others that are biallelic. Our data suggest that wild-type JAK3 competes with mutant JAK3 (M511I) for binding to the common chain and thereby suppresses its oncogenic potential. We demonstrate that JAK3 (M511I) can increase its limited oncogenic potential through the acquisition of an additional mutation in the mutant JAK3 allele. These double JAK3 mutants show increased STAT5 activation and increased potential to transform primary mouse pro–T cells to interleukin-7–independent growth and were not affected by wild-type JAK3 expression. These data extend our insight into the oncogenic properties of JAK3 mutations and provide an explanation of why progression of JAK3-mutant T-ALL cases can be associated with the accumulation of additional JAK3 mutations.
Degryse, S., Bornschein, S., de Bock, C. E., Leroy, E., Vanden Bempt, M., Demeyer, S., Jacobs, K., Geerdens, E., Gielen, O., Soulier, J., Harrison, C. J., Constantinescu, S. N., Cools, J.
American Society of Hematology (ASH)
0006-4971
00064971
1528-0020
15280020
shingle_title_1 Mutant JAK3 signaling is increased by loss of wild-type JAK3 or by acquisition of secondary JAK3 mutations in T-ALL
shingle_title_2 Mutant JAK3 signaling is increased by loss of wild-type JAK3 or by acquisition of secondary JAK3 mutations in T-ALL
shingle_title_3 Mutant JAK3 signaling is increased by loss of wild-type JAK3 or by acquisition of secondary JAK3 mutations in T-ALL
shingle_title_4 Mutant JAK3 signaling is increased by loss of wild-type JAK3 or by acquisition of secondary JAK3 mutations in T-ALL
timestamp 2025-06-30T23:32:15.451Z
titel Mutant JAK3 signaling is increased by loss of wild-type JAK3 or by acquisition of secondary JAK3 mutations in T-ALL
titel_suche Mutant JAK3 signaling is increased by loss of wild-type JAK3 or by acquisition of secondary JAK3 mutations in T-ALL
topic W
WW-YZ
uid ipn_articles_6146206