In the introduction of the paper on Acute Myeloid Leukemia (AML), the researchers presented information regarding what this disease was and how the genes associated with having this disease correlates with certain mutations. AML is a rapidly growing form of blood/bone marrow cancer; it arises when a person’s stem cells, specified for the production of blood, grow abnormally. Over time, researchers have been able to locate driver mutations for this form of cancer, however, the number of genes and mutations continue to grow as the disease evolves. This led the researchers of the paper to conduct three clinical trials in which they made a comprehensive study of AML genes within various age groups of people with the disease.
To prepare for their clinical trials, the research team gathered samples from three groups of patients who had AML. One group of patients were between the ages of 18 to 65, the next group between 18 to 61, and the final group was between 58 to 84 years old. For the genetic profiling of their trials, they used cytogenetic analyses to look within cells and sequenced 111 genes in the process. To help guide them on what to look for when reviewing the genes from the samples, they based their analysis on various ideas of what they considered driver mutations. This included aneuploidies, leukemia gene mutations such as deletions or insertions, and fusion genes. For their statistical analysis, they used a method known as the Bayesian Dirichlet process to organize their data from each subgroup and to make classification rules.
Some of the overarching results from their trials were that they found over 5000 driver mutations within 76 genes from 1540 patients. Out of these mutations identified, they saw that around 73% of these mutations were point mutations and found within patients who had severe cases of AML. One specific gene that they highlighted was the NPM1 gene which paired with NRASG12/13 gene often; ultimately meaning that some of the genes function together for co-mutations. These findings led to the implication that the more driver mutations found within patients would correlate with their survival rate regardless of age. They also saw that within their data that any mutations related to transcriptional regulators, splicing, or within chromatin influenced the survival rate of patients with AML.
Within their discussion of the trials and data found within them, they reviewed their results about the different genes found within the subgroups of patients and a few genes that were found in large percentages of the patients. They reiterated that the more driver mutations found had effects on the rate of survival. Of the three genomic categories presented within their data, the chromatin-spliceosome category was representative of the largest portion of the patients within their trials.
References:
Papaemmanuil, E. et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med 374(23). doi: 10.1056/NEJMoa1516192 (2016).