Overexpression of GADD45g inhibits proliferation and invasion of acute myeloid leukemia cell lines with FLT3-ITD+ by downregulating the JNK pathway

To Explore the effects of overexpression of GADD45g inhibits proliferation and invasion of acute myeloid leukemia (AML) cell lines with FLT3-ITD ⁺ by downregulating the JNK pathway. A total of 30 bone marrow specimens from patients with initial diagnosis of AML were selected, of which 10 were FLT3-ITD ⁺ , and the expression level of GADD45G mRNA was detected by Real-time PCR in bone marrow single nuclei from patients with primary AML, FLT3-ITD ⁺ AML patients, as well as FLT3-ITD ⁺ AML cell lines. GADD45G overexpression lentivirus was constructed and infected FLT3-ITD ⁺ AML cell lines, and the effects of GADD45G overexpression on FLT3 ⁺ AML cell lines were analyzed by CCK-8 assay, invasive migration, colony formation and flow assay. The effect on biological functions after using the JNK pathway inhibitor SP600125. The expression level of GADD45G was significantly lower in FLT3-ITD ⁺ AML patients and cell lines ( P < 0.001). Overexpression of GADD45G in FLT3-ITD ⁺ AML cell lines inhibited cell proliferation, migration and invasion, clone formation ( P <0.001) and induced apoptosis ( P <0.001), and significantly increased the expression levels of P-JNK/JNK and P-P38/P38 proteins ( P <0.001). The use of JNK pathway inhibitor SP600125 promoted proliferation, migration invasion, clone formation, inhibited apoptosis ( P <0.001) and decreased expression of related proteins ( P <0.001) compared with the overexpression of GADD45G group. The GADD45G gene is lowly expressed in bone marrow and cell lines of FLT3-ITD ⁺ AML patients, which inhibits their biological functions, and the overexpression of GADD45G may induce apoptosis by downregulating the JNK pathway.