Genetic alterations in Guatemalan acute myeloid leukemia patients

Abstract

Context: Acute myeloid leukemia (AML) is a cancer in which the three hematopoietic lines are altered: erythroid, myeloid and megakaryocytic line. In this type of leukemia, we have found a variety of genetic markers that allow better management of the disease. The translocation t (8; 21) (q22; q22), which causes the transcript AML1-ETO, the t (15; 17) (q22; q21), which causes the transcript PML-RARA and inv (16) (p13; q22) that leads to the transcribed CBFB-MYH11; have good prognosis. Even the presence of the PML-RARA transcript directed to a specific treatment, that is the combination of trans- retinoic acid with chemotherapy. Furthermore mutations in FLT3 and cKIT genes; and monosomies on chromosome 7 and 5; confer a poor prognosis when they are present in acute myeloid leukemia. Objective: The main aim of this study was to assess the frequency of the main genetic alterations that have been found worldwide related to acute myeloid leukemia in Guatemalan population. Design and Patients: We collected 129 bone marrow samples from patients with a diagnosis of AML referred from different national hospitals. Every patient signed the informed consent form approved by the local ethics committee. For the identification for all the genetic alterations, we use a combination of various techniques such as PCR, SANGER sequencing and FISH. Results: The PML-RARA transcript was the most frequent alteration found in our population (14%) and was found in 87% of patients with AML M3; as it has been reported in other countries. This was followed by the AML1-ETO transcript, which was found in 9%. The third most frequent was the FLT3 internal tandem duplication mutation in 10% of patients. We have found only two patients with the V826 mutation in exon 17 of c-KIT; two patients with monosomy 7 and one patient with the inv(16) (p13q22). Additionally, we have found several co-expressions: two patients who have PML-RARa transcript and FLT3 ITD mutation; two patients with PML-RARa and FLT3 D835 mutation, one patient with the AML1-ETO transcript and c-KIT exon 17 mutation; and one patient with monosomy 7 and AML1-ETO presence. These coexpressions have been reported with low incidence in other countries. Conclusion: The genetic alteration co-expressions in AML are rare events that can occur in this pathology. We found 6 patients with two genetic markers, one of good prognosis and one poor prognosis. Keywords: genetic, alteration, acute, myeloid, leukemia.