Objective To explore the expression patterns of inhibitor of differentiation (ID) family in patients with chronic myeloid leukemia (CML) and analyze their clinical implications.

Methods Quantitative PCR and quantitative methylation-specific PCR were conducted to detect the transcript levels of ID2/ID3/ID4 and the methylation levels of ID4 in the bone marrow mononuclear cells of non-hematological malignancies (acting as controls) and patients with CML treated at The Affiliated People’s Hospital of Jiangsu University from January 2010 to December 2017. The clinical implications of ID family alterations were further analyzed.

Results ID2 and ID3 expression was significantly up regulated (P<0.001 and P<0.05, respectively), whereas ID4 expression was markedly down regulated in patients with CML (P<0.01). The receiver operating characteristic curve demonstrated that the ID2 transcript level is a potential biomarker for distinguishing CML from controls (AUC=0.895, P<0.001). The frequency of ID4 promoter methylation in patients with CML was drastically higher than that in the controls (P=0.001). Moreover, ID4 methylation was negatively correlated with ID4 expression in patients with CML (r=−0.424, P=0.002). Clinically, CML with high ID2 expression occurred more frequently in males (P=0.040). Patients with low ID4 expression or high ID4 methylation showed a markedly higher frequency of an accelerated phase/blast crisis (P=0.003 and P<0.001, respectively). In addition, patients with CML in an accelerated phase/blast crisis exhibited markedly lower ID4 expression and higher ID4 methylation levels than those in the chronic phase (both P<0.001). Furthermore, univariate and multiple Logistic regression analyses revealed that the ID4 methylation level was an independent risk factor for CML progression (P=0.007).

Conclusions The ID family was differentially expressed in patients with CML; specifically, ID2 and ID3 expression was significantly increased, whereas ID4 expression was markedly decreased and correlated with ID4 promoter hypermethylation. Hence, ID4 expression and methylation are confirmed to be associated with CML progression, and ID4 methylation could be an independent risk factor for CML progression.