TY - JOUR
T1 - PDE4 Differential Expression Is a Potential Prognostic Factor and Therapeutic Target in Patients With Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia
AU - Chamseddine, Ali N.
AU - Cabrero, Monica
AU - Wei, Yue
AU - Ganan-Gomez, Irene
AU - Colla, Simona
AU - Takahashi, Koichi
AU - Yang, Hui
AU - Bohannan, Zachary S.
AU - Garcia-Manero, Guillermo
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - PDE4 expression control the inflammation which has an essential role in the pathogenesis of myelodysplastic syndromes (MDS). The expression of each isoform of the PDE4 was evaluated, using transcriptomic profiling, from healthy individuals (n = 10) and patients with MDS (n = 24) or chronic myelomonocytic leukemia (n = 19). PDE4 mean expression was generally higher in MDS than in healthy individuals. Higher PDE4 expression seemed to have a possible negative effect on survival and response to hypomethylating agent (P > .05). Background (or Purpose) Inflammation has an essential role in the pathogenesis of myelodysplastic syndromes (MDS). Its expression is controlled by phosphodiesterase 4 (PDE4). Thus, PDE4 inhibitors might be useful therapeutic targets for MDS. Patients (or Materials) and Methods We evaluated the expression of each isoform of PDE4 (A, B, C, and D) using transcriptomic profiling and examined the potential impact on the outcome of patients with MDS in terms of survival and response to hypomethylating agents. Total RNA was extracted from CD34+ bone marrow hematopoietic cells from healthy individuals (n = 10) and patients with MDS (n = 24) or chronic myelomonocytic leukemia (n = 19). Results The study cohort had a median follow-up period of 21.2 months (range, 0.2-68 months) and a median overall survival of 17.6 months (95% confidence interval, 9.6-25.6). The main finding of the present study was that PDE4 mean expression was generally higher in patients with MDS than in healthy individuals. Also, upregulated PDE4 expression seemed to have a possible negative effect on survival (P > .05). Moreover, lower, compared with higher, mean PDE4A and PDE4C expression is indicative of a response to a hypomethylating agent (0.09 and 0.03 vs. 0.54 and 0.49, respectively; P > .05). Conclusion These results should be confirmed in a larger patient cohort. PDE4 expression could be an effective potential prognostic factor and therapeutic target for patients with MDS and chronic myelomonocytic leukemia. The role of PDE4 inhibitors should be explored in vitro against MDS cell lines and in preclinical mouse models of MDS.
AB - PDE4 expression control the inflammation which has an essential role in the pathogenesis of myelodysplastic syndromes (MDS). The expression of each isoform of the PDE4 was evaluated, using transcriptomic profiling, from healthy individuals (n = 10) and patients with MDS (n = 24) or chronic myelomonocytic leukemia (n = 19). PDE4 mean expression was generally higher in MDS than in healthy individuals. Higher PDE4 expression seemed to have a possible negative effect on survival and response to hypomethylating agent (P > .05). Background (or Purpose) Inflammation has an essential role in the pathogenesis of myelodysplastic syndromes (MDS). Its expression is controlled by phosphodiesterase 4 (PDE4). Thus, PDE4 inhibitors might be useful therapeutic targets for MDS. Patients (or Materials) and Methods We evaluated the expression of each isoform of PDE4 (A, B, C, and D) using transcriptomic profiling and examined the potential impact on the outcome of patients with MDS in terms of survival and response to hypomethylating agents. Total RNA was extracted from CD34+ bone marrow hematopoietic cells from healthy individuals (n = 10) and patients with MDS (n = 24) or chronic myelomonocytic leukemia (n = 19). Results The study cohort had a median follow-up period of 21.2 months (range, 0.2-68 months) and a median overall survival of 17.6 months (95% confidence interval, 9.6-25.6). The main finding of the present study was that PDE4 mean expression was generally higher in patients with MDS than in healthy individuals. Also, upregulated PDE4 expression seemed to have a possible negative effect on survival (P > .05). Moreover, lower, compared with higher, mean PDE4A and PDE4C expression is indicative of a response to a hypomethylating agent (0.09 and 0.03 vs. 0.54 and 0.49, respectively; P > .05). Conclusion These results should be confirmed in a larger patient cohort. PDE4 expression could be an effective potential prognostic factor and therapeutic target for patients with MDS and chronic myelomonocytic leukemia. The role of PDE4 inhibitors should be explored in vitro against MDS cell lines and in preclinical mouse models of MDS.
KW - Chronic myelomonocytic leukemia (CMML)
KW - Inflammation
KW - Myelodysplastic syndromes (MDS)
KW - Phosphodiesterase 4 (PDE4)
KW - Prognosis
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U2 - 10.1016/j.clml.2016.02.026
DO - 10.1016/j.clml.2016.02.026
M3 - Article
C2 - 27521329
AN - SCOPUS:84992065809
SN - 2152-2650
VL - 16
SP - S67-S73
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
ER -