HLA-DPA1*/DPB1* en asociación con leucemias linfoides agudas y leucemias mieloides crónicas en mestizos venezolanos / HLA-DPA1*/DPB1* in association with acute lymphoid leukemias and chronic myeloid leukemias patients in Venezuelan twins

RESUMEN

Hoy conocemos algo más de la participación de la región HLA-DP en la patogénesis de las leucemias gracias a varios estudios demostrando la injerencia temprana de estas moléculas en la modulación de la respuesta inmunitaria frente a patógenos. Para la evaluación de alelos y haplotipos HLA-DPA1*/DPB1* (28 alelos del locus HLA-DPA1* y 123 alelos HLA-DPB1*) se utilizó PCR SSPTM Olerup (Genovision) en 48 pacientes con LLA, 48 con LMC y 48 controles mestizos venezolanos. Para la asociación HLA/leucemias se tomó el riesgo relativo (RR) > 3 como positivo y negativo RR < 3, con una p corregida < 0,05. Pacientes LLA confirmaron asociaciones positivas con el alelo DPA1*0105 y negativa con el alelo DPA1*010301-010302. Además, resultaron asociados positivamente DPA1*0106 y *0107; DPA1*020101-020106 se asoció negativamente con la LLA. DPA1*0105, *0108 y *0109 resultaron asociados negativamente con la LMC. Las frecuencias observadas de los alelos HLA-DPB1*0101, 0201, 0301, 0401 y 0402 en los controles mestizos venezolanos ubicadas entre 7 y 16% fueron superiores a las de pacientes leucémicos. Se confinaron asociaciones negativas de los alelos DPB1*0201 y DPB1*0301 con las LLA. No se observaron asociaciones positivas con las LLA. DPB1*9901 se asoció negativamente con las LLA. La región DPB1* sola no parece estar asociada a las leucemias en esta población venezolana. La fuerte asociación LMC con varios haplotipos DPA/DPB indica importantes diferencias entre las patogénesis de ambas enfermedades

ABSTRACT

More is now known of the involvement of HLA-DP region in the pathogenesis of the leukemias through several previousstudies showing interference of these molecules in modulating the immune response to pathogens. For evaluation of HLA alleles and haplotypes DPA1*/DPB1* (28 alleles HLA DPA1* and 123 of HLA- DPB1*) Olerup SSP ™PCR (Genovision) was used in 48 patients with ALL, 48 CML, and 48 Venezuelan twins as controls. For HLA/leukemias, a relative risk (RR) > 3 was considered to be a positive association and negative with an RR<3, with a p corrected P<.05. ALL patients confirmed positive associations with DPA1*0105 allele, and negative with DPA1*010301-010302. In addition, they were positively associated with DPA1*0106 and *0107, with DPA1*020101-020106 being negatively associated with ALL. DPA1*0105, *0108 and *0109 were negatively associated with CML. The observed frequencies of HLA-DPB1* 0101, 0201, 0301, 0401 and 402 alleles in Venezuelan, which twins were between 7 and 16%, were higher than those of leukemic patients. Negative associations of DPB1*201, *301 and LLA were confined. No positive associations were observed with ALL. Non-confirmed positive associations were observed between DPB1*9901 and CML. Haplotypes HLA-DPA1*0103-DPB1*401, *201, *9901 were strongly positively associated with CML. DPA1*109-DPB1*201, *401 were negatively associated with the CML. DPA1*103-DPB1*402; DPA1*0109-DPB1*201, *401 and DPA1*0201-DPB1*0402 were negatively associated with ALL. The DPB1* single region does not appear to be associated with leukemia in the Venezuelan population. The strong association with several haplotypes DPA*1/DPB1* and LMC suggests massive differences between the pathogenesis of both diseases