New Study Investigates CSF3R Mutations in Acute Myeloid Leukemia


Investigations into the CSF3R gene may help lead to better classification and precise treatment of AML.

Researchers report that they are moving closer toward understanding the pathogenesis of acute myeloid leukemia (AML). In the journal Cancer, they write that investigations into the CSF3R gene may help lead to better classification and precise treatment of AML, and could provide useful guidance for targeted therapy.

Yang Zhang, MD, of the division of pathology and laboratory medicine at Hebei Yanda Lu Daopei Hospital in Langfang, China, and colleagues report that the CSF3R gene encodes the colony-stimulating factor 3 receptor, and that this is essential for the production, differentiation, and function of granulocytes. Among patients with chronic neutrophilic leukemia, approximately 83% have CSF3R mutations, which serve as a specific diagnostic marker. However, CSF3R mutations are uncommon in AML.

Zhang et al report that when CSF3R mutations occur in patients with AML, they are often associated with core-binding factor gene abnormalities and double-mutated CCAAT/enhancer binding protein α (CEBPAdm). They theorize that an in-depth understanding of the interaction between these genetic alterations could provide a better picture of the role of CSF3R mutations in AML development.

The researchers retrospectively conducted amplicon-targeted, next-generation sequencing of 58 genes in 1,152 patients (587 AML patients and 565 with acute lymphoid leukemia [ALL]). The team used reverse transcriptase-polymerase chain reaction to detect 35 leukemia-specific gene fusions. The primary goal of this investigation was to assess the incidence of CSF3R mutations in acute leukemia and their association with other genetic abnormalities.

The study showed that 26 patients had CSF3R mutations. Among the 26 cases, 13 of the 364 patients with de novo AML had the mutation (3.6%), and 8 of the 175 patients with relapsed AML had the mutation (4.6%). These mutations were also found in 4 of 48 patients with secondary AML (8.3%), and in 1 of 565 ALL patients (0.2%). Among the 26 patients, the researchers detected a total of 9 distinct CSF3R mutations. They also identified membrane‐proximal missense mutations and cytoplasmic truncations as being mutually exclusive.

A few interesting findings turned up when the researchers looked at the number of patients who had French-American-British subtypes M2 and M4. The French-American-British subtypes M2 and M4 were significantly more common in the CSF3R-mutated group than the CSF3R wild‐type group for both the de novo AML cohort (P = .001) and the relapsed AML cohort (P = .024). The researchers found that all the CSF3R mutations in the de novo and relapsed AML cohorts were associated with specific genetic alterations in transcription factors, including RUNX1-RUNX1T1, CBFB-MYH11, CEBPAdm, and NPM1 mutations.

In this investigation, the team was able to combine high-throughput DNA sequencing technologies, bioinformatics, and detailed clinical and patient information to provide a more precise understanding of the nature of CSF3R mutations in AML. They also identified the interactions of these mutations with other genetic abnormalities.

Henry Chi Hang Fung, MD, vice chair of the department of hematology/oncology at Fox Chase Cancer Center in Philadelphia, said a greater understanding of gene mutations is significant and may lead to new treatments. However, he said there are many hurdles that will still need to be overcome. “We still have a long way to go to understand gene mutations. We are learning more,” he said in an interview with Cancer Network. “It is an exciting time for researchers, but not the patients yet.”

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