Low 25(OH) vitamin D₃ levels are associated with adverse outcome in newly diagnosed, intensively treated adult acute myeloid leukemia

Abstract

Background Several studies suggest that low 25(OH) vitamin D3 levels may be prognostic in some malignancies, but no studies have evaluated their impact on treatment outcome in acute myeloid leukemia (AML). Methods VD levels were evaluated in 97 consecutive newly diagnosed, intensively-treated AML patients. MicroRNA-expression profiles and single nucleotide polymorphisms (SNPs) in the 25(OH) vitamin D3 pathway genes were evaluated and correlated with 25(OH) vitamin D3 levels and treatment outcome. Results Thirty-four (35%) patients had normal 25(OH) vitamin D3 levels (32–100 ng/ml), 34 (35%) insufficient (20–31.9 ng/ml) and 29 (30%) deficient levels (<20 ng/ml). Insufficient/deficient 25(OH) vitamin D3 levels were associated with worse relapse-free survival (RFS) compared to normal vitamin D3 levels. In multivariate analyses, deficient 25(OH) vitamin D3, smoking, European LeukemiaNet Genetic Groups and white blood cell count retained their statistical significance for RFS. A number of microRNAs and SNPs were found to be associated with 25(OH) vitamin D3 level, although none remained significant after multiple test corrections; one 25(OH) vitamin D3 receptor SNP, rs10783219, was associated with lower complete remission rate (p=0.0442), shorter RFS (p=0.0058) and overall survival (p=0.0011). Conclusions It remains to be determined what role microRNA and SNP profiles play in contributing to low 25(OH) vitamin D3 level and/or outcome and whether supplementation will improve AML outcome.

Impact of p53 Status on Radiosensitization of Tumor Cells by MET Inhibition–Associated Checkpoint Abrogation

“…Inhibition of CHK1 in various cancer types harboring p53 mutation including breast cancer, multiple myeloma, colon carcinoma, pancreatic cancer, and brain glioblastoma resulted in cell death mainly via mitotic catastrophe when simultaneously exposed to DNA damage. Currently, several CHK1 inhibitors (e.g., Sch 900776, GDC0425, GDC0575) are evaluated in clinical trials, highlighting the therapeutic advantage and benefits of a checkpoint abrogation approach in anticancer treatment (48)(49)(50).…”

Vitamin D and Acute Myeloid Leukemia

“…Therefore, supplementation and corollary studies are needed to understand the effect of vitamin D on hematologic malignancies. Lee et al (Lee, HJ 2010) have recently reported 25(OH)D 3 levels at the time of diagnosis of AML and their association with survival. A cohort of 97 newly diagnosed AML patients treated on similar protocols showed that patients with subnormal 25(OH)D 3 (<32ng/ml) had significantly worse progression free survival (PFS) and OS when compared to those with normal 25(OH)D 3 levels (≥32ng/ml) (Figure 1).…”

“…There are several reports (Drake, Maurer et al 2010;Lee HJ 2010;Shanafelt, Drake et al 2011) indicating that low levels of vitamin D have been shown to be associated with worse clinical outcome; however, there are no prospective studies evaluating whether supplementation would improve outcome. It would be worthwhile to conduct a trial studying the effect of vitamin D supplementation in newly diagnosed AML patients.…”

“…Three studies have shown the prognostic significance of vitamin D deficiency in hematologic malignancies, including CLL (Shanafelt, Drake et al 2011), NHL (Drake, Maurer et al 2010) and AML (Lee HJ 2010). There have been no studies evaluating the clinical significance of vitamin D supplementation on raising the 25(OH)D 3 levels of patients with hematologic malignancies to normal.…”

“…Vitamin D insufficiency as serum 25(OH)D 3 between 10-32ng/ml (25-75 nmol/L) (Rosen 2011). Subnormal vitamin D levels as less than 32 ng/ml of 25(OH)D 3 (Lee, HJ 2010). There are currently no standards of measurement or methods to measure vitamin D levels in the clinical setting.…”