IGF-IR determines the fates of BCR/ABL leukemia

Xie, Jingjing; Chen, Xiaoli; Zheng, Junke; Li, Chunling; Stacy, Satomi; Holzenberger, Martin; Hu, Xuemei; Zhang, Cheng Cheng

doi:10.1186/s13045-015-0106-8

Cited by 18 publications

(12 citation statements)

References 43 publications

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“…In the pre-TKI era, the prognosis of BCR-ABL-positive B-ALL has been shown to be extremely unfavorable with 7 years of OS <50 % [ 10 ]. Recently, loss of tyrosine kinase receptor in Ph-positive cells was found to result in the development of ALL [ 11 ]. The development of TKIs has also been reported to markedly improve the outcome of Ph-positive ALL [ 12 – 14 ].…”

Section: Discussionmentioning

confidence: 99%

Correlation between deletion of the CDKN2 gene and tyrosine kinase inhibitor resistance in adult Philadelphia chromosome-positive acute lymphoblastic leukemia

et al. 2016

J Hematol Oncol

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BackgroundFrequency relapses are common in Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) following tyrosine kinase inhibitors (TKIs). CDKN2A/B is believed to contribute to this chemotherapy resistance.MethodsTo further investigate the association between CDKN2 status and TKI resistance, the prevalence of CDKN2 deletions and its correlation with a variety of clinical features was assessed in 135 Ph-positive ALL patients using interphase fluorescence in situ hybridization (I-FISH).ResultsResults showed that no difference occurred between patients with CDKN2 deletion (44/135) and wild-type patients in sex, age, and complete remission (CR) rate following induction chemotherapy combined with tyrosine kinase inhibitors (TKIs). However, CDKN2 deletion carriers demonstrated higher white blood cell (WBC) count, enhanced rates of hepatosplenomegaly (P = 0.006), and upregulation of CD20 expression (P = 0.001). Moreover, deletions of CDKN2 resulted in lower rates of complete molecular response (undetectable BCR/ABL), increased cumulative incidence of relapse, short overall survival (OS), and disease-free survival (DFS) time (P < 0.05) even though these patients received chemotherapy plus TKIs followed by allogenic hematopoietic stem cell transplantation (Allo-HSCT). In the case of 44 patients who presented with CDKN2 deletion, 18 patients were treated with dasatinib treatment, and another 26 patients were treated with imatinib therapy, and our study found that there were no differences associated with OS (P = 0.508) and DFS (P = 0.555) between the two groups.ConclusionsCDKN2 deletion is frequently acquired during Ph-positive ALL progression and serves as a poor prognostic marker of long-term outcome in Ph-positive ALL patients with CDKN2 deletion even after the second-generation tyrosine kinase inhibitor treatment.

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Section: Discussionmentioning

confidence: 99%

Correlation between deletion of the CDKN2 gene and tyrosine kinase inhibitor resistance in adult Philadelphia chromosome-positive acute lymphoblastic leukemia

et al. 2016

J Hematol Oncol

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“…For retrovirus production, human embryonic kidney 293T cells were grown in DMEM with 10% fetal bovine serum (FBS) and transfected by MSCV-MLL-AF9-IRES-YFP, MSCV-CAMKIV-IRES-GFP, MSCV-CAMKI-IRES-GFP, or MSCV-CREB-IRES-GFP encoding plasmids and pCL-ECO to produce retroviruses. The infection of Linage-negative cells with retrovirus was performed as described previously [ 1 , 15 , 16 ]. Briefly, we infected Lin − cells with retroviral supernatant in the presence of 8 μg/mL polybrene.…”

Section: Methodsmentioning

confidence: 99%

“…We performed flow cytometry, immunohistochemistry, and cytospin as described previously [ 1 , 15 , 16 ]. For flow cytometry analysis of AML cells, peripheral blood or BM cells were stained with anti-Mac-1-APC, anti-Gr-1-PE, anti-CD3-APC, anti-B220-PE, or anti-Kit-PE monoclonal antibodies (BioLegend).…”

Section: Methodsmentioning

confidence: 99%

CAMKs support development of acute myeloid leukemia

et al. 2018

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BackgroundWe recently identified the human leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse ortholog-paired Ig-like receptor (PirB) as receptors for several angiopoietin-like proteins (Angptls). We also demonstrated that PirB is important for the development of acute myeloid leukemia (AML), but exactly how an inhibitory receptor such as PirB can support cancer development is intriguing.ResultsHere, we showed that the activation of Ca (2+)/calmodulin-dependent protein kinases (CAMKs) is coupled with PirB signaling in AML cells. High expression of CAMKs is associated with a poor overall survival probability in patients with AML. Knockdown of CAMKI or CAMKIV decreased human acute leukemia development in vitro and in vivo. Mouse AML cells that are defective in PirB signaling had decreased activation of CAMKs, and the forced expression of CAMK partially rescued the PirB-defective phenotype in the MLL-AF9 AML mouse model. The inhibition of CAMK kinase activity or deletion of CAMKIV significantly slowed AML development and decreased the AML stem cell activity. We also found that CAMKIV acts through the phosphorylation of one of its well-known target (CREB) in AML cells.ConclusionCAMKs are essential for the growth of human and mouse AML. The inhibition of CAMK signaling may become an effective strategy for treating leukemia.Electronic supplementary materialThe online version of this article (10.1186/s13045-018-0574-8) contains supplementary material, which is available to authorized users.

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“…Lentivirus infection was performed essentially as we described [[22,25]][22,26,27]. The lentiviral vector Pll3.7 was used to express shRNAs designed to target adcy7 mRNA.…”

Section: Methodsmentioning

confidence: 99%

ADCY7 supports development of acute myeloid leukemia

Chen

Yin

et al. 2015

Biochemical and Biophysical Research Communications

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Acute myeloid leukemia (AML) is the most common adult acute leukemia. Despite treatment, the majority of the AML patients relapse within 5 years. In silico analysis of several available databases of AML patients showed that the expression of adenylate cyclase 7 (ADCY7) significantly inversely correlates with the overall survival of AML patients. To determine whether ADCY7 supports AML development, we employed an shRNA-encoding lentivirus system to inhibit adcy7 expression in human AML cells including U937, MV4-11, and THP-1 cells. The ADCY7 deficiency resulted in decreased cell growth, elvated apoptosis, and lower c-Myc expression of these leukemia cells. This indicates that G protein-coupled receptor signaling contributes to AML pathogenesis. Our study suggests that inhibition of ADCY7 may be novel strategy for treating leukemia.

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IGF-IR determines the fates of BCR/ABL leukemia

Cited by 18 publications

References 43 publications

Correlation between deletion of the CDKN2 gene and tyrosine kinase inhibitor resistance in adult Philadelphia chromosome-positive acute lymphoblastic leukemia

Correlation between deletion of the CDKN2 gene and tyrosine kinase inhibitor resistance in adult Philadelphia chromosome-positive acute lymphoblastic leukemia

CAMKs support development of acute myeloid leukemia

ADCY7 supports development of acute myeloid leukemia

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