2. Academic Validation
  3. Spermatogenesis associated serine rich 2 like plays a prognostic factor and therapeutic target in acute myeloid leukemia by regulating the JAK2/STAT3/STAT5 axis

Spermatogenesis associated serine rich 2 like plays a prognostic factor and therapeutic target in acute myeloid leukemia by regulating the JAK2/STAT3/STAT5 axis

  • J Transl Med. 2023 Feb 11;21(1):115. doi: 10.1186/s12967-023-03968-0.
Fenglin Li # 1 2,  Wenle Ye # 1,  Yiyi Yao # 1,  Wenwen Wei 1,  Xiangjie Lin 1,  Haihui Zhuang 2,  Chenying Li 1 3,  Xia Li 1 3,  Qing Ling 1,  Chao Hu 1 3,  Xin Huang 1 3,  Yu Qian 1,  Shihui Mao 1,  Jiansong Huang 1 3,  Ying Lu 4,  Jie Jin 5 6 7
Affiliations

Affiliations

  • 1 Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Qingchun road 79#, Hangzhou, China.
  • 2 Department of Hematology, The Affiliated People's Hospital of Ningbo University, Baizhang road 251#, Ningbo, China.
  • 3 Zhejiang Provincial Key Lab of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China.
  • 4 Department of Hematology, The Affiliated People's Hospital of Ningbo University, Baizhang road 251#, Ningbo, China. [email protected].
  • 5 Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Qingchun road 79#, Hangzhou, China. [email protected].
  • 6 Zhejiang Provincial Key Lab of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China. [email protected].
  • 7 Zhejiang University Cancer Center, Hangzhou, China. [email protected].
  • # Contributed equally.
PMID: 36774517 DOI: 10.1186/s12967-023-03968-0
Abstract

Background: Spermatogenesis associated serine rich 2 like (SPATS2L) was highly expressed in homoharringtonine (HHT) resistant acute myeloid leukemia (AML) cell lines. However, its role is little known in AML. The present study aimed to investigate the function of SPATS2L in AML pathogenesis and elucidate the underlying molecular mechanisms.

Methods: Overall survival (OS), event-free survival (EFS), relapse-free survival (RFS) were used to evaluate the prognostic impact of SPATS2L for AML from TCGA database and ourcohort. ShRNA was used to knockdown the expression of SPATS2L. Apoptosis was assessed by flow cytometry. The changes of proteins were assessed by Western blot(WB). A xenotransplantation mice model was used to evaluate in vivo growth and survival. RNA sequencing was performed to elucidate the molecular mechanisms underlying the role of SPATS2L in AML.

Results: SPATS2L expression increased with increasing resistance indexes(RI) in HHT-resistant cell lines we had constructed. Higher SPATS2L expression was observed in intermediate/high-risk patients than in favorable patients. Meanwhile, decreased SPATS2L expression was observed in AML patients achieving complete remission (CR). Multivariate analysis showed high SPATS2L expression was an independent poor predictor of OS, EFS, RFS in AML. SPATS2L knock down (KD) suppressed cell growth, induced Apoptosis, and suppressed key proteins of JAK/STAT pathway, such as JAK2, STAT3, STAT5 in AML cells. Inhibiting SPATS2L expression markedly enhanced the pro-apoptotic effects of traditional chemotherapeutics (Ara-c, IDA, and HHT).

Conclusions: High expression of SPATS2L is a poor prognostic factor in AML, and targeting SPATS2L may be a promising therapeutic strategy for AML patients.

Keywords

AML; Apoptosis; Growth; JAK/STAT pathway; Prognostic; SPATS2L; Therapeutic target.

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