Microsatellite instability and cytogenetic survey in myeloid leukemias

Abstract

Microsatellites are short tandem repeat sequences dispersed throughout the genome. Their instability at multiple genetic loci may result from mismatch repair errors and it occurs in hereditary nonpolyposis colorectal cancer. This instability is also found in many sporadic cancers. In order to evaluate the importance of this process in myeloid leukemias, we studied five loci in different chromosomes of 43 patients, 22 with chronic myelocytic leukemia (CML) in the chronic phase, 7 with CML in blast crisis, and 14 with acute myeloid leukemia (AML), by comparing leukemic DNA extracted from bone marrow and constitutional DNA obtained from buccal epithelial cells. Only one of the 43 patients (2.1%), with relapsed AML, showed an alteration in the allele length at a single locus. Cytogenetic analysis was performed in order to improve the characterization of leukemic subtypes and to determine if specific chromosome aberrations were associated with the presence of microsatellite instability. Several chromosome aberrations were observed, most of them detected at diagnosis and during follow-up of the patients, according to current literature. These findings suggest that microsatellite instability is an infrequent genetic event in myeloid leukemias, adding support to the current view that the mechanisms of genomic instability in solid tumors differ from those observed in leukemias, where specific chromosome aberrations seem to play a major role.

Detection of mutator phenotype in Brazilian patients with acute and chronic myeloid leukemia

“…However, there was no statistical difference from some frequencies reported earlier by Wada et al (1994), Pabst et al (1996), Tasaka et al (1997), Das-Gupta et al (2001) and Ribeiro et al (2002), whose findings demonstrated MSI in patients with myeloid leukemia. A statistical difference was also observed between the LOH frequency reported by Boyer et al (1998) for the marker BAT-26 in AML patients and the frequency found in this study.…”

“…Moreover, an increased incidence of adverse cytogenetic abnormalities has been found in AML patients with MSI, and even a patient with favorable cytogenetic findings, but with MSI, was reported to have had early relapse of AML (Das-Gupta et al, 2001). In contrast, in CML patients, MSI has been identified as an uncommon event (Mori et al, 1997;Auner et al, 1999;Ribeiro et al, 2002), although there is one former report suggesting that MSI may occur as a late event in the evolution of CML toward blast crisis (Wada et al, 1994). In conformity with these previous findings, which correlate MSI and mutator phenotype with a more aggressive progression of AML, the prognosis of our AML patient (A11) with MSI-H was poor.…”

“…This disagreement may be due to the number of patients studied, panel of markers chosen, MSI assessment criteria, source of non-tumoral control sample or methodological differences (Wada et al, 1994;Pabst et al, 1996;Mori et al, 1997;Tasaka et al, 1997;Boyer et al, 1998;Auner et al, 1999;Rimsza et al, 2000;Das-Gupta et al, 2001;Ribeiro et al, 2002). In this context, considering the scarcity of reports regarding such frequencies in Brazil, we aimed to investigate microsatellite alterations and the role of the mutator phenotype in a group of Brazilian patients with myeloid leukemia.…”

Short tandem repeat and human leukocyte antigen mutations or losses confound engraftment and typing analysis in hematopoietic stem cell transplants

“…Microsatellite instability has been described during the early phases of disease [18] for multiple hematological malignancies, including AML/MDS, during progression [4] and in therapy-related circumstances [19]. However, studies have suggested that in comparison with solid tumors, microsatellite instability is an infrequent genetic event in myeloid malignancies [20]. In this report, we have described 5 AML/MFIB patients, 4 with LOH in STR alleles and 1 with an STR length mutation.…”