Bin Yin

Background: Acute myeloid leukemia (AML) is an aggressive cancer with variable treatment responses. While clinical factors such as age and genetic mutations contribute to prognosis, recent studies suggest that CT attenuation scores may also predict treatment outcomes. This study aims to develop a nomogram combining clinical and CT-based factors to predict treatment response and guide personalized therapy for AML patients. Methods: This retrospective study included 74 newly diagnosed AML patients who underwent unenhanced abdominal CT scans within one week before receiving their first induction chemotherapy. Clinical biomarkers of tumor burden were also collected. Patients were classified into two groups based on treatment response: complete remission (CR; n = 24) and non-complete remission (NCR; n = 50). Multivariable logistic regression was used to identify independent predictors of treatment response. Predictive performance was evaluated using receiver operating characteristic (ROC) curves, and model consistency was assessed through calibration and decision curve analysis (DCA). Results: Significant differences in hemoglobin (Hb), platelets (Plt), and CT attenuation scores were observed between the CR and NCR groups (all p < 0.05). Multivariable logistic regression identified Hb, Plt, and CT attenuation scores as independent predictors of treatment response. A nomogram incorporating these factors demonstrated excellent predictive performance, with an area under the curve (AUC) of 0.912 (95% CI: 0.842–0.983), accuracy of 0.865 (95% CI: 0.765–0.933), sensitivity of 0.880 (95% CI: 0.790–0.970), and specificity of 0.833 (95% CI: 0.684–0.982). The CR nomogram displayed significant clinical value and excellent goodness of fit. Conclusions: The nomogram, which incorporates Hb, Plt, and CT attenuation scores, provides valuable insights into predicting treatment response in AML patients. This model offers strong discriminatory ability and could enhance personalized treatment planning and prognosis prediction for AML.

Resistance to cytarabine is an important cause of therapy failure in persons with acute myeloid leukemia (AML). Deoxycytidine kinase, encoded by DCK, catalyzes phosphorylation of cytarabine to cytarabine monophosphate, a necessary step for eventual incorporation of cytarabine triphosphate into DNA and for clinical efficacy. Whether DCK mutations make AML cells resistant to cytarabine is controversial. We studied DCK mutations and messenger RNA (mRNA) concentrations in leukemia cells from 10 subjects with AML who received cytarabine-based therapy and relapsed and in 2 artificially induced cytarabine-resistant AML cell lines. DCK mutations were detected in 4 subjects with AML relapsing after achieving a complete remission and receiving high-dose cytarabine postremission therapy. Most mutations were in exons 4–6 and were not present before therapy. DCK was also mutated in cytarabine-resistant but not parental AML cell lines. DCK mRNA concentrations were significantly decreased in cytarabine-resistant K562 and SHI-1 cells compared with cytarabine-sensitive parental cells. Mutation frequency of DCK and mRNA concentration did not correlate with the extent of cytarabine resistance indicating other factors operate. Overexpression of wild-type DCK restored cytarabine sensitivity to previously resistant leukemia cell lines. Our data contribute to the understanding of cytarabine resistance in persons with AML.

The mechanisms underlying acute myeloid leukemia (AML) treatment failure are not clear. Here, we established a mouse model of AML by syngeneic transplantation of BXH-2 derived myeloid leukemic cells and developed an efficacious Ara-C-based regimen for treatment of these mice. We proved that leukemic cell load was correlated with survival. We also demonstrated that the susceptibility of leukemia cells to Ara-C could significantly affect the survival. To examine the molecular alterations in cells with different sensitivity, genome-wide expression of the leukemic cells was profiled, revealing that overall 366 and 212 genes became upregulated or downregulated, respectively, in the resistant cells. Many of these genes are involved in the regulation of cell cycle, cellular proliferation, and apoptosis. Some of them were further validated by quantitative PCR. Interestingly, the Ara-C resistant cells retained the sensitivity to ABT-737, an inhibitor of anti-apoptosis proteins, and treatment with ABT-737 prolonged the life span of mice engrafted with resistant cells. These results suggest that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C. Incorporation of apoptosis inhibitors, such as ABT-737, into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C. This work provided direct in vivo evidence that leukemic load and intrinsic cellular resistance can affect the outcome of AML treated with Ara-C, suggesting that incorporation of apoptosis inhibitors into traditional cytotoxic regimens merits consideration for the treatment of AML in a subset of patients with resistance to Ara-C.