Differential profile of CDKN1A and TP53 expressions in bone marrow mesenchymal stromal cells from myeloid neoplasms

Attention has been increasing focused on the role of the bone marrow microenvironment in the pathogenesis and progression of hematological malignancies, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).1–3 Thus, the identification of genes or proteins that are differentially expressed in the abnormal bone marrow niche may provide new therapeutic opportunities and perspectives on the biology of these diseases. In a recent report by Fei et al.,4 bone marrow mesenchymal stromal cells (BMMSCs) from MDS patients presented an upregulation of p21 and p53 expressions, suggesting that activation of this pathway may contribute to the senescent behavior of these cells.4 In contrast, another study that also analyzed the expression profile of senescence-related genes in BMMSCs from MDS and healthy donors observed a downregulation of CDKN1A expression, but no modulation in TP53 expression.5 To provide additional evidence on p21 and p53 expression in MDS BMMSCs, we verified the expression of these genes in a cohort of eight healthy donors with median age of 45 years (range: 28–57), 23 MDS patients with median age of 70 years (range: 16–90), seven AML patients with myelodysplasia-related changes (AML-MRC) with median age of 69 years (range: 30–86) and 12 de novo AML cases according to the WHO 2008 classification, with median age of 61 years (range: 44–82).6 The MDS group was comprised of one refractory cytopenia with unilineage dysplasia (RCUD), four refractory anemia with ringed sideroblasts (RARS), 12 refractory cytopenia with multilineage dysplasia (RCMD), two refractory anemia with excess blast-1 (RAEB-1) and four refractory anemia with excess blast-2 (RAEB-2). Bone marrow mononuclear cells were isolated by Ficoll-Hypaque plus density-gradient centrifugation (GE Healthcare, Uppsala, Sweden) and cultured in Dulbecco’s Modified Eagle’s Medium (DMEM; Gibco, Grand Island, NY, USA) supplemented with 10% fetal bovine serum (FBS), penicillin/streptomycin and lasms