An immunological approach to acute myeloid leukaemia

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• 作者：B. Gonzá ; lez^a ; D. Bueno^a ; P.M. Rubio^a ; S. San Romá ; n^a ; D. Plaza^a ; A. Sastre^a ; P. Garcí ; a-Miguel^a ; L. Ferná ; ndez^b ; J. Valentí ; n^c ; I. Martí ; nez^d ; A. Pé ; rez-Martí ; nez^a ; ^c ; ^{aperezmartinez@salud.madrid.org" class="auth_mail" title="E-mail the corresponding author} ; ^{antonioperezmartinez@yahoo.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Acute myeloid leukaemia ; Natural killer cells ; Human leucocyte antigen class I (HLA-I) ; Major histocompatibility complex (MHC) class-I related chain A/B (MICA/B) ; UL16-binding proteins 1-4 (ULBP 1-4)
• 刊名：Anales de Pediatría (English Edition)
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：84
• 期：4
• 页码：195-202
• 全文大小：923 K

文摘

Acute myeloid leukaemia (AML) is the second haematological malignancy in the paediatric population, and one of the leading causes of childhood cancer mortality. Survival is currently around 60%, with no improvement in last decades, suggesting that new therapeutic approaches are needed. The anti-leukaemia effect mediated by the lymphocytes and natural killer (NK) cells of the immune system has been established in haematopoietic stem cell transplantation, and also as adoptive immunotherapy after consolidation chemotherapy schemes.

Patients and methods

A retrospective study was conducted on the clinical characteristics of patients diagnosed and treated for AML in our centre from 1996 to 2014. The mean fluorescence intensities of HLA-I, MICA/B and ULBP1-4, ligands for NK cell receptors, were also analysed in ten new diagnosed leukaemia cases, five myeloid and five lymphoid.

Results

A total of 67 patients were used in this analysis. With a median follow up of 25 months, the event-free survival was 62% (95% CI: 55–67). Secondary AML, non-M3 phenotype, and the absence of favourable cytogenetic markers had a lower survival. The probability of relapse was 38% (95% CI: 31–45). The expression of HLA-I and ULBP-4 was significantly lower in myeloid than in lymphoid blast cells.

Conclusions

Our clinical results are similar to those described in the literature. Survival did not significantly change in recent decades, and the likelihood of relapse remains high. Myeloid blasts might be more susceptible to the cytotoxicity of NK cells through their lower expression of HLA-I. NK therapy strategies in minimal disease situation could be effective, as reported by other groups.