More on Geographic Hematology: The Breakpoint Cluster Regions of the PML/RARα Fusion Gene in Mexican Mestizo Patients with Promyelocytic Leukemia are Different from Those in Caucasians

Abstract

Acute promyelocytic leukemia is characterized the PML/RARalpha chimeric fusion gene, transcript and protein; the breakpoint cluster regions (bcr) in the PML gene may occur in 3 different sites: Intron 6 (bcr1), exon 6 (bcr2) or intron 3 (bcr3). In a 10-year period in a single institution, we studied prospectively the breakpoint cluster regions of the PML/RARalpha fusion gene in 43 Mexican Mestizo patients with APL, and found that the bcr1 represented 62.7%, the bcr2 9.3% whereas the bcr3 27.9%. The prevalence of the bcr1 subtype is significantly higher than that informed in Caucasians and similar to that in Asians; these data are consonant with those described in other Latin-American patients with APL. Since other Asian genetic markers have been found in the Indian component of the Mexican mestizos, it is possible that the Asian immigration into the Americas through the strait of Behring 12,000 years ago may account for a possible genetic susceptibility to suffer certain forms of APL.

Improving acute promyelocytic leukemia (APL) outcome in developing countries through networking, results of the International Consortium on APL

“…The frequency of the breakpoint cluster region 1 (bcr1) PML/RARA isoform was not increased compared with that reported in Europe, which contrasts with previous studies analyzing patients from Latin America. [30][31][32] This difference, however, likely reflects the distinct geographical and ethnic origin of patients in the 2 reported series (eg, Mexican mestizos by Santos et al 28 and mostly Brazilian in this study). Immunofluorescence staining using the anti-PML antibody was adopted as a rapid diagnostic method that could be performed at all centers and did not require a sophisticated infrastructure.…”

Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007

“…30 Investigations of 3 breakpoint sites (bcr1, bcr2, and bcr3) of the PML gene involved in APL with t(15;17), have described significantly higher prevalence of bcr1 among individuals from Latin America compared with published reports of non-Latino populations in the United States and Europe. 31,32 In addition, several recent genome-wide association studies of childhood ALL/L have identified risk loci with varying effects by racial/ethnic group for B-and T-cell ALL/L, 33,34 further highlighting the importance of considering disease subtypes according to race/ethnicity and age in etiologic investigations.…”

Do paradigma molecular ao impacto no prognóstico: uma visão da leucemia promielocítica aguda

“…Porém, a real incidência da LPA não é conhecida, e a maioria dos estudos baseia-se em registros hospitalares. Existe, ainda, uma variabilidade genética correlacionada à distribuição geográfica, com diferentes freqüências das isoformas do PML-RARα conforme a população estudada [25][26][27] .…”