INTRODUCTION:
Therapy related myelodysplastic syndrome and acute myeloid leukemia acute myeloid leukemia: (uh-KYOOT my-uh-LOYD loo-KEE-mee-uh) A cancer of the blood cells. It happens when very young white blood cells (blasts) in the bone marrow fail to mature. The blast cells stay in the bone marrow and become to numerous. This slows production of red blood cells and platelets. Some cases of MDS become… (t-MDS/AML) are defined as complications of previous cytotoxic therapy. Azacitidine Azacitidine: It works by reducing the amount of methylation in the body. Methylation is a process that acts like a switch to turn off or “silence” genes in certain cells. When these genes (called tumor suppressor genes) are turned off, MDS cells and cancer cells can grow freely. Azacitidine is approved by the U… (AZA), a hypomethylating agent, has showed activity in t-MDS/AML.
OBJECTIVES:
We evaluated the clonal dynamics of AZA treated t-MDS/AML.
METHODS:
We collected bone marrow bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow. samples, at diagnosis and during treatment, from AZA-treated t-MDS/AML patients. NGS on 19 myeloid genes was performed and candidate mutations with a variant allele frequency >5 % were selected.
RESULTS:
7 t-AML and 12 t-MDS were included with median age of 71 (56-82) years old, median number of AZA cycles of 6 (1-15) and median overall survival (OS) of 14 (3-29) months. We observed correlation between AZA response and clonal selection. Decrease of TP53 mutated clone clone: To make copies. Bone marrow stem cells clone themselves all the time. The cloned stem cells eventually become mature blood cells that leave the bone marrow and enter the bloodstream. was correlated with response to AZA, confirming AZA efficacy in this subgroup. In some patients, emergence of mutations was correlated with progression or relapse without impact on OS. Clones with mutations in genes for DNA methylation regulation frequently occurred with other mutations and remained stable during AZA treatment, independent of AZA response.
CONCLUSION:
We confirmed the molecular complexity of t-MNs and that the follow-up of clonal selection during AZA treatment could be useful to define treatment combination.