Potential role of autophagy induced by FLT3-ITD and acid ceramidase in acute myeloid leukemia chemo-resistance: new insights

Zalpoor H., Bakhtiyari M., Akbari A., Aziziyan F., Shapourian H., Liaghat M., ...Daha Fazla

Cell Communication and Signaling, cilt.20, sa.1, 2022 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 20 Sayı: 1
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1186/s12964-022-00956-7
  • Dergi Adı: Cell Communication and Signaling
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, EMBASE, MEDLINE, Directory of Open Access Journals
  • Anahtar Kelimeler: Acid ceramidase, Acute myeloid leukemia, Autophagy, Chemo-resistance, FLT3-ITD, Sphingosine
  • İstanbul Medipol Üniversitesi Adresli: Hayır

Özet

Acute myeloid leukemia (AML) is a type of leukemia with a poor prognosis and survival characterized by abnormal cell proliferation and differentiation. Despite advances in treatment, AML still has a low complete remission rate, particularly in elderly patients, and recurrences are frequently seen even after complete remissions. The major challenge in treating AML is the resistance of leukemia cells to chemotherapy drugs. Thus, to overcome this issue, it can be crucial to conduct new investigations to explore the mechanisms of chemo-resistance in AML and target them. In this review, the potential role of autophagy induced by FLT3-ITD and acid ceramidase in chemo-resistance in AML patients are analyzed. With regard to the high prevalence of FLT3-ITD mutation (about 25% of AML cases) and high level of acid ceramidase in these patients, we hypothesized that both of these factors could lead to chemo-resistance by inducing autophagy. Therefore, pharmacological targeting of autophagy, FLT3-ITD, and acid ceramidase production could be a promising therapeutic approach for such AML patients to overcome chemo-resistance.