TY - JOUR
T1 - Jak3 activation is significantly associated with ALK expression in anaplastic large cell lymphoma
AU - Lai, Raymond
AU - Rassidakis, George Z.
AU - Lin, Quan
AU - Atwell, Coralyn
AU - Medeiros, L. Jeffrey
AU - Amin, Hesham M.
PY - 2005/9
Y1 - 2005/9
N2 - Janus kinase 3 (Jak3) is a tyrosine kinase that activates signal transducer and activator of transcription 3 (Stat3) in response to cytokine stimulation. Stat3 is an oncogene. In previous studies of anaplastic large cell lymphoma (ALCL), we showed that inhibition of Jak3 down-regulates activated/ phosphorylated Stat3 (pStat3), decreases anaplastic lymphoma kinase (ALK) enzymatic activity, and induces cell-cycle arrest and apoptosis in ALK-positive ALCL. These findings implicate Jak3 as playing a significant role in the pathogenesis of ALK-positive ALCL; most likely via Stat3 and ALK activation. To assess this possibility, we used immunohistochemical staining to evaluate the frequency of expression of Jak3 and its activated/phosphorylated form (pJak3) in 48 systemic ALCL tumors included in a tissue microarray. pJak3 was detected in 17 (81%) of 21 ALK-positive tumors, compared with 3 (11%) of 27 ALK-negative tumors (P < .0001, Fisher exact test). pStat3 was present in 12 (86%) of 14 ALK-positive tumors and in 10 (40%) of 25 ALK-negative tumors assessed (P = .0078). Of 12 ALK-positive/pStat3-positive tumors, 8 (67%) expressed pJak3, but none of 10 ALK-negative/pStat3-positive tumors expressed pJak3. We conclude that Jak3 activation is predominantly restricted to ALK-positive ALCL tumors. Most likely, Jak3 collaborates with ALK in activating Stat3, leading to cell survival, cell-cycle progression, and tumor growth. In contrast, the mechanism of Stat3 activation in ALK-negative ALCL tumors appears to be independent of Jak3.
AB - Janus kinase 3 (Jak3) is a tyrosine kinase that activates signal transducer and activator of transcription 3 (Stat3) in response to cytokine stimulation. Stat3 is an oncogene. In previous studies of anaplastic large cell lymphoma (ALCL), we showed that inhibition of Jak3 down-regulates activated/ phosphorylated Stat3 (pStat3), decreases anaplastic lymphoma kinase (ALK) enzymatic activity, and induces cell-cycle arrest and apoptosis in ALK-positive ALCL. These findings implicate Jak3 as playing a significant role in the pathogenesis of ALK-positive ALCL; most likely via Stat3 and ALK activation. To assess this possibility, we used immunohistochemical staining to evaluate the frequency of expression of Jak3 and its activated/phosphorylated form (pJak3) in 48 systemic ALCL tumors included in a tissue microarray. pJak3 was detected in 17 (81%) of 21 ALK-positive tumors, compared with 3 (11%) of 27 ALK-negative tumors (P < .0001, Fisher exact test). pStat3 was present in 12 (86%) of 14 ALK-positive tumors and in 10 (40%) of 25 ALK-negative tumors assessed (P = .0078). Of 12 ALK-positive/pStat3-positive tumors, 8 (67%) expressed pJak3, but none of 10 ALK-negative/pStat3-positive tumors expressed pJak3. We conclude that Jak3 activation is predominantly restricted to ALK-positive ALCL tumors. Most likely, Jak3 collaborates with ALK in activating Stat3, leading to cell survival, cell-cycle progression, and tumor growth. In contrast, the mechanism of Stat3 activation in ALK-negative ALCL tumors appears to be independent of Jak3.
KW - ALK
KW - Anaplastic large cell lymphoma
KW - Jak3
KW - Stat3
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U2 - 10.1016/j.humpath.2005.07.011
DO - 10.1016/j.humpath.2005.07.011
M3 - Article
C2 - 16153455
AN - SCOPUS:24344472670
SN - 0046-8177
VL - 36
SP - 939
EP - 944
JO - Human Pathology
JF - Human Pathology
IS - 9
ER -