The SKM-1 Leukemic Cell Line Established from a Patient with Progression to Myelomonocytic Leukemia in Myelodysplastic Syndrome (MDS)-Contribution to Better Understanding of MDS

Abstract

Although molecular and cytogenetic studies strongly point to the role of oncogenes, the mechanisms underlying the development of MDS and their progressive evolution to AML are still largely unknown. It has been postulated that AML has a preleukemic stage and a multi step pathogenesis, with the preleukemic stem cell able to undergo clonal evolution, with the acquisition of karyotypic abnormalities, leading to the development of acute leukemic subclones. The activations of the ras oncogenes or inactivation of the p53 anti-oncogene by point mutations have been described recently in several cases of MDS as well as AML, suggesting a critical role for these alterations in the development of these myelogenous leukemias. We reported previously establishment of a leukemic cell line, SKM-1, from the patient who initially possessed multiple point mutations of ras genes but lost these mutations during disease progression to myelomonocytic leukemia with acquisition of chromosomal abnormalities involving the p53 anti-oncogene. This process is characterized by genetic instabilities probably due to the failure of their DNA repairment leading to abnormal control of cell proliferation and differentiation. Studying this cell line, SKM-1, is a promising approach to understand the mechanisms of the initiation, disease progression, alterations of DNA repairment, and genetic instability in MDS and myelogenous malignancies.

Ribosomal protein L23 negatively regulates cellular apoptosis via the RPL23/Miz-1/c-Myc circuit in higher-risk myelodysplastic syndrome

“…To the best of our knowledge, the SKM-1 cell line, which was established in the leukaemic phase during the progression from MDS to AML, is karyotypically abnormal (including a 17p deletion) and is characteristic of the acquisition of p53 mutations (missense and silent point mutations) 30, 31 . Mutation of the p53 gene is associated with complex karyotypes, reduces overall survival and plays a role in the evolution of MDS to AML 30–32 . Therefore, the loss of normal p53 gene function, i.e., the allelic inactivation of 17p and the point mutation of the other allelic p53 gene in the SKM-1 cell line, might give rise to undetected p53 alterations and RPL23-HDM2-p53 signal activation, as previously reported.…”

Sequential combination of decitabine and idarubicin synergistically enhances anti-leukemia effect followed by demethylating Wnt pathway inhibitor promoters and downregulating Wnt pathway nuclear target

“…SKM-1 was established from a patient with progression to myelomonocytic leukemia in MDS, which was defined as refractory leukemia cell line [13]. It was obtained from the Health Science Research Resources Bank (Osaka, Japan).…”

Synergistic inhibitory effects of deferasirox in combination with decitabine on leukemia cell lines SKM-1, THP-1, and K-562

“…Nakagawa et al . believe that this cell line may contribute to understanding the pathogenesis of MDS and its leukemic progression [20]. …”