Selective inhibition of JAK2-Driven erythroid differentiation of polycythemia vera progenitors

被引：112

作者：

Geron, Ifat ^{[1
]}

Abrahamsson, Annelie E. ^{[1
]}

Barroga, Charlene F. ^{[1
]}

Kavalerchik, Edward ^{[1
]}

Gotlib, Jason ^{[2
]}

Hood, John D. ^{[3
]}

Durocher, Jeffrey ^{[4
]}

Mak, Chi Ching ^{[3
]}

Noronha, Glenn ^{[3
]}

Soll, Richard M. ^{[3
]}

Tefferi, Ayalew ^{[5
]}

Kaushansky, Ken ^{[1
]}

Jamieson, Catriona H. M. ^{[1
]}

机构：

[1] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[2] Stanford Univ, Dept Med, Stanford, CA 94305 USA

[3] TargeGen Inc, San Diego, CA 92121 USA

[4] Transgenomic Inc, Gaithersburg, MD 20878 USA

[5] Mayo Clin, Dept Med, Rochester, MN 55905 USA

来源：

CANCER CELL | 2008年 / 13卷 / 04期

关键词：

D O I：

10.1016/j.ccr.2008.02.017

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Polycythemia Vera (PV) is a myeloproliferative disorder (MPD) that is commonly characterized by mutant JAK2 (JAK2V617F) signaling, erythrocyte overproduction, and a propensity for thrombosis, progression to myelofibrosis, or acute leukemia. In this study, JAK2V617F expression by human hematopoietic progenitors promoted erythroid colony formation and erythroid engraftment in a bioluminescent xenogeneic immunocompromised mouse transplantation model. A selective JAK2 inhibitor, TG1 01348 (300 nM), significantly inhibited JAK2V617F(+) progenitor-derived colony formation as well as engraftment (120 mg/kg) in xenogeneic transplantation studies. TG1 01348 treatment decreased GATA-1 expression, which is associated with erythroid-skewing of JAK2V617F(+) progenitor differentiation, and inhibited STAT5 as well as GATA S310 phosphorylation. Thus, TG1 01348 may be an effective inhibitor of JAK2V617F(+) MPDs in clinical

引用

页码：321 / 330

页数：10

共 39 条

[1] POLYCYTHEMIA-VERA - STEM-CELL AND PROBABLE CLONAL ORIGIN OF DISEASE
ADAMSON, JW
FIALKOW, PJ
MURPHY, S
PRCHAL, JF
STEINMANN, L
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 1976, 295 (17) : 913 - 916
[2] Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders
Baxter, EJ
Scott, LM
Campbell, PJ
East, C
Fourouclas, N
Swanton, S
Vassiliou, GS
Bench, AJ
Boyd, EM
Curtin, N
Scott, MA
Erber, WN
Green, AR
[J]. LANCET, 2005, 365 (9464) : 1054 - 1061
[3] Lentivirally transduced dendritic cells as a tool for cancer immunotherapy
Breckpot, K
Dullaers, M
Bonehill, A
Van Meirvenne, S
Heirman, C
De Greef, C
van der Bruggen, P
Thielemans, K
[J]. JOURNAL OF GENE MEDICINE, 2003, 5 (08) : 654 - 667
[4] UNREGULATED PROLIFERATION OF PRIMITIVE NEOPLASTIC PROGENITOR CELLS IN LONG-TERM POLYCYTHEMIA-VERA MARROW CULTURES
CASHMAN, JD
EAVES, CJ
EAVES, AC
[J]. JOURNAL OF CLINICAL INVESTIGATION, 1988, 81 (01) : 87 - 91
[5] DAI CH, 1992, BLOOD, V80, P891
[6] INDUCTION OF CHRONIC MYELOGENOUS LEUKEMIA IN MICE BY THE P210BCR/ABL GENE OF THE PHILADELPHIA-CHROMOSOME
DALEY, GQ
VANETTEN, RA
BALTIMORE, D
[J]. SCIENCE, 1990, 247 (4944) : 824 - 830
[7] Deconinck AE, 2000, DEVELOPMENT, V127, P2031
[8] Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia
Druker, Brian J.
Guilhot, Francois
O'Brien, Stephen G.
Gathmann, Insa
Kantarjian, Hagop
Gattermann, Norbert
Deininger, Michael W. N.
Silver, Richard T.
Goldman, John M.
Stone, Richard M.
Cervantes, Francisco
Hochhaus, Andreas
Powell, Bayard L.
Gabrilove, Janice L.
Rousselot, Philippe
Reiffers, Josy
Cornelissen, Jan J.
Hughes, Timothy
Agis, Hermine
Fischer, Thomas
Verhoef, Gregor
Shepherd, John
Saglio, Giuseppe
Gratwohl, Alois
Nielsen, Johan L.
Radich, Jerald P.
Simonsson, Bengt
Taylor, Kerry
Baccarani, Michele
So, Charlene
Letvak, Laurie
Larson, Richard A.
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (23) : 2408 - 2417
[9] FIALKOW PJ, 1981, BLOOD, V58, P916
[10] CHRONIC MYELOCYTIC-LEUKEMIA - CLONAL ORIGIN IN A STEM-CELL COMMON TO GRANULOCYTE, ERYTHROCYTE, PLATELET AND MONOCYTE-MACROPHAGE
FIALKOW, PJ
JACOBSON, RJ
PAPAYANNOPOULOU, T
[J]. AMERICAN JOURNAL OF MEDICINE, 1977, 63 (01) : 125 - 130

← 1 2 3 4 →