Association of HLA antigens and BCR-ABL transcripts in leukemia patients with the Philadelphia chromosome

Abstract

Objective This study aimed to verify the association between human leukocyte antigens and the bcr-abl fusion protein resulting from t(9;22)(q34;q11) in chronic leukemia myeloid and acute lymphoblastic leukemia patients. Methods Forty-seven bcr-abl positive individuals were evaluated. Typing was performed bymicrolymphocytotoxicity and molecular biological methods (human leukocyte antigens Class I and Class II). A control group was obtained from the data of potential bone marrow donors registered in the Brazilian Bone Marrow Donor Registry (REDOME). Results Positive associations with HLA-A25 and HLA-B18 were found for the b2a2 transcript, as well as a tendency towards a positive association with HLA-B40 and a negative association with HLA-A68. The b3a2 transcript showed positive associations with HLA-B40 and HLA-DRB1*3. Conclusion The negative association between human leukocyte antigens and the BCR-ABL transcript suggests that binding and presentation of peptides derived from the chimeric protein are effective to increase a cytotoxic T lymphocyte response appropriate for the destruction of leukemic cells.

Comparative Gene Expression Analysis Reveals Similarities and Differences of Chronic Myeloid Leukemia Phases

“…Further, an in-depth literature analysis revealed that several of these genes play important roles in cancer ( CDCA3 [ 26 ], ECEL1 [ 27 ], EN1 [ 28 ], HLA-DMB [ 29 , 30 ], SPRR2A [ 31 ], TMEM40 [ 32 , 33 , 34 ]) including acute myeloid leukemia ( CDCA3 [ 35 ], HLA-DMB [ 30 ], RPL18A [ 36 ], PF4 [ 37 , 38 ], PRG3 [ 39 ]) and T cell acute lymphoblastic leukemia ( TLX3 [ 40 ]). Moreover, some of these genes have already been reported to play a role in CML ( AURKB [ 41 ], AZU1 [ 42 , 43 ], HLA-B [ 44 ], HLA-DMB [ 30 ], PF4 [ 45 ]). In addition, a subset of these genes has been associated with cancer therapy responses ( AZU1 [ 42 , 43 ], CDCA3 [ 26 ], CEACAM6 [ 46 ], EN1 [ 28 ], PF4 [ 37 , 38 , 45 ]).…”

Frecuencia de los transcriptos p190BCR-ABL y p210BCR-ABL en una población colombiana con leucemia mieloide crónica (LMC) usando RT-PCR cualitativa

“…Se hicieron comparaciones de las frecuencias de las fusiones génicas que codifican para el transcripto p210 (b3a2, b2a2 y la coexpresión b3a2/b2a2) con las informadas en la literatura en trabajos similares. En el análisis de los resultados, de las ocho poblaciones informadas solo tres fueron estadísticamente significativas (13)(14)(15)(16)(17). Para el transcripto b3a2 fueron significativas las diferencias con las poblaciones europea, paquistaní y cubana (10,12,15) en relación a la estudiada en este trabajo, y para el transcripto b2a2 no se hallaron diferencias significativas (tabla 2).…”

BCR-ABL rearrangement and HLA antigens: a possible link to leukemia pathogenesis and immunotherapy

“…In this perspective,even if it is well known that different populations show different HLA haplotype frequencies, the findings of Carvalho et al (4) , trying to unravel the issue of the association of HLA molecules with BCR-ABL peptides inside the Brazilian population, have the major advantage of raising novel interests about the immune pathogenesisof CML and the CML immune-mediated therapies. In fact, the Carvalho et al report indicates that BCR-ABL peptides may be presented by different HLA molecules, which inside the specific CML population may elicit a productive (negative association) or ineffective (positive association) binding to leukemic proteins, in comparison with the healthy population.…”

“…Other scientific studies report analyses of the association between particular HLA alleles and different types of BCR-ABL fusion proteins at a population level, assuming that a negative association of a particular BCR-ABL product with specific HLA alleles suggests that these alleles play a critical role in presenting peptides derived from the chimeric proteins and in eliciting a successful T lymphocyte cytotoxic response ( 3 ) . In this perspective,even if it is well known that different populations show different HLA haplotype frequencies, the findings of Carvalho et al ( 4 ) , trying to unravel the issue of the association of HLA molecules with BCR-ABL peptides inside the Brazilian population, have the major advantage of raising novel interests about the immune pathogenesisof CML and the CML immune-mediated therapies. In fact, the Carvalho et al report indicates that BCR-ABL peptides may be presented by different HLA molecules, which inside the specific CML population may elicit a productive (negative association) or ineffective (positive association) binding to leukemic proteins, in comparison with the healthy population.…”

“…In fact, the Carvalho et al report indicates that BCR-ABL peptides may be presented by different HLA molecules, which inside the specific CML population may elicit a productive (negative association) or ineffective (positive association) binding to leukemic proteins, in comparison with the healthy population. Carvalho et al showed a positive association between HLA-A25 and HLA-B18 as well as a negative association between HLA-A68 and e13a2 transcripts,whereas they reported a positive association between HLA-B40 and HLA-DRB1*3 with e14a2 transcripts ( 4 ) . On the basis of positive/negative associations, it has been assumed that HLA-restricted Tlymphocyte cytotoxicity accomplishes an immunosurveillance role in the pathogenesis of BCR-ABL leukemias.…”