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Novel HLA-C*06:02:01:94 and -C*15:02:01:58 alleles were detected during the routine HLA typing process., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel HLA-B*15:665 and HLA-C*12:02:02:23 alleles were detected during the routine HLA typing process., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel HLA-A*01:01:01:111 allele was detected during routine HLA typing., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel HLA-B*40:01:02:59 and HLA-C*05:01:73 alleles were detected during the routine HLA typing process., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Acute Myeloid Leukemia (AML) is a complex disease with rapid progression and poor/unsatisfactory outcomes. In the past few years, the focus has been on developing newer therapies for AML; however, relapse remains a significant problem. Natural Killer cells have strong anti-tumor potential against AML. This NK-mediated cytotoxicity is often restricted by cellular defects caused by disease-associated mechanisms, which can lead to disease progression. A stark feature of AML is the low/no expression of the cognate HLA ligands for the activating KIR receptors, due to which these tumor cells evade NK-mediated lysis. Recently, different Natural Killer cell therapies have been implicated in treating AML, such as the adoptive NK cell transfer, Chimeric antigen receptor-modified NK (CAR-NK) cell therapy, antibodies, cytokine, and drug treatment. However, the data available is scarce, and the outcomes vary between different transplant settings and different types of leukemia. Moreover, remission achieved by some of these therapies is only for a short time. In this mini-review, we will discuss the role of NK cell defects in AML progression, particularly the expression of different cell surface markers, the available NK cell therapies, and the results from various preclinical and clinical trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 D’Silva, Singh and Pinto.)

Novel HLA-A*33:03:62, -B*52:01:01:25 alleles and confirmatory HLA-A*02:01:209 allele were detected during the HLA typing process., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel alleles HLA-DQA1*01:01:01:11 and -DQA1*01:03:01:13 were detected during the routine HLA typing process., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel allele HLA-C*07:02:01:184 as compared with HLA-C*07:02:01:03 displays polymorphism at position; gDNA 2896 (G > C)., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel HLA-B*58:01:01:19 allele was characterized using next generation sequencing technology., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel allele, HLA-B*40:02:01:39 differs from the HLA-B*40:02:01:01 allele by a single nucleotide change at gDNA position 700., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel HLA-DPA1*01:03:01:64 allele was detected during routine HLA typing., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel allele HLA-A*24:02:01:136 as compared with HLA-A*24:02:01:01 displays a single nucleotide polymorphism at position; gDNA 2827 (C > A)., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel HLA-DQA1*01:01:01:10 allele differs from HLA-DQA1*01:01:01:07 by a single nucleotide change at gDNA 702 G T., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel allele HLA-B*37:01:01:19 differs from B*37:01:01:01 by one nucleotide A->G in Intron 3 at gDNA1430., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel allele HLA-A*11:01:01:86 differs from HLA-A*11:01:01:86 by one nucleotide change at position; gDNA-32 (A- > C)., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel HLA-C*12:02:47 allele was detected during routine HLA typing., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Relationship between various combinations of KIR ligands and HLA alleles have been studied in several diseases. The aim of this retrospective study was to estimate the frequency of HLA alleles and KIR ligands among acute myeloid leukemia patients and healthy controls in order to examine the possible association of HLA alleles and KIR ligands with AML. A total of 439 acute myeloid leukemia patients and 1317 unrelated, healthy ethnic Indian controls were included in the study. HLA typing was performed using PCR-SSP. KIR ligands were assigned by using the KIR ligand Calculator. The frequency of HLA alleles and KIR ligands in patients was then compared with the controls. As compared to controls, frequencies of HLA-A*03 and HLA-B*35 were increased in AML patients, whereas, that of HLA-C*03 was decreased. Frequencies of HLA-A*03 and HLA-C*15 were increased in male patients, however, no significant difference was observed in female patients as compared to controls. In the pediatric group, the frequencies of HLA-A*01 was decreased and that of HLA-A*03 and HLA-B*18 were increased, whereas, frequencies of HLA-B*13 was decreased and that of HLA-B*27 was increased in the adult patients. In the haplotype analysis, the frequency of HLA-A*24/B*35/DRB1*15 was increased in overall patients. In adult group, the frequency of HLA-A*01/B*44/DRB1*07 was increased in patients than in controls. No significant association was observed between KIR ligands and susceptibility/ protection to AML. Our results indicate that certain HLA alleles and haplotypes have presumptive positive or negative role in conferring protection/susceptibility to AML., Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01550-0., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Author(s), under exclusive licence to Indian Society of Hematology and Blood Transfusion 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

HLA-DPA1*02:82 differs from DPA1*02:01:01:02 by a single nucleotide at gDNA 4890 in exon 4., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel allele HLA-C*06:02:38:02 differs from HLA-C*06:02:38:01 by a nucleotide change at position; gDNA 168 T ➔ A., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel HLA-B*52:01:01:23 allele differs from HLA-B*52:01:01:01 by a nucleotide change at gDNA-61 C➔A., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel HLA-DQB1*06:01:01:04 allele was detected during routine HLA typing., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel allele HLA-C*03:599 as compared with HLA-C*03:04:01:02 displays polymorphism at position; gDNA 1618 (G>T)., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel allele HLA-A*02:11:01:06 as compared with HLA-A*02:11:01:01 displays polymorphism at position; gDNA 1562 (C>A)., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-C*07:04:01:19 differs from C*07:04:01:01 by one nucleotide change in gDNA at position 2420 in intron 5., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel allele HLA-DQB1*04:02:01:18 differs from HLA-DQB1*04:02:01:04 by a nucleotide change at position; gDNA 2789 A → G., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-A*11:03:01:02 differs from HLA-A*11:03:01:01 by one nucleotide change at gDNA position 1280 in the intron 3., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-DRB1*14:245 differs from DRB1*14:54:01:01 by one nucleotide change in gDNA at position 7898 in exon 3., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The HLA-B*51:01:01:108 and HLA-B*40:387 alleles were detected during routine HLA typing., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel alleles HLA-A*68:175:02 and -A*68:287 each differ from -A*68:01:02:02 by a single nucleotide., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

HLA-DRB1*14:50:02 differs from DRB1*14:04:03 by one nucleotide change in codon 77 in exon 2., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel allele HLA-C*04:01:01:129 as compared to HLA-C*04:01:01:01 displays polymorphism at two positions; gDNA 2905 (C → T) and 2910 (T → A)., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel allele HLA-DPB1*02:01:61 as compared with HLA-DPB1*02:01:02 displays polymorphism by a single nucleotide at gDNA 9011 C->T., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel HLA-B*51:01:01:83 allele differs from HLA-B*51:01:01:01 by A- > G nucleotide substitution at gDNA 2569., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel HLA-B*52:01:01:18 allele differs from HLA-B*52:01:01:02 by A→C nucleotide change at gDNA -155., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel HLA-B*13:02:01:18 allele differs from HLA-B*13:02:01:01 by A->G nucleotide change at gDNA 2477., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel HLA-C*04:01:01:102 allele differs from HLA-C*04:01:01:01 by G → A nucleotide change at gDNA 2591., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel HLA-C*14:02:01:22 allele differs from HLA-C*14:02:01:01 by a nucleotide change at gDNA -156 C → T., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The novel HLA-A*24:537 allele differs from HLA-A*24:02:01:01 by a nucleotide change at gDNA 294 C → T., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

One hundred and sixty one healthy unrelated hematopoietic stem cell transplant donors from Western Indian were enrolled in this study. The study was initiated to observe the genotypic diversity of 16 killer immunoglobulin like receptor (KIR) genes in this population. KIR genotyping was carried out using the PCR-SSP technique. 56 KIR genotypes were observed in our population, where 15 genotypes were reported for the first time in any population. The KIR genotype data for the population can be accessed from Allele Frequencies Net Database under the population name "India Western KIR" and identifier "3570"., (Copyright © 2019. Published by Elsevier Inc.)

The present study was undertaken to investigate genetic variations present in the coding regions of the UGT1A1 gene among the Gilbert's syndrome patients. Analysis of genetic variations was performed by direct DNA sequencing among the patients that do not have any polymorphic variations in the promoter regions of the UGT1A1 gene. We identified seven different sequence variations among Gilbert's Syndrome patients, of which four were novel. Out of seven variants, six missense and one silent single nucleotide substitutions were present in the UGT1A1 gene. In addition, molecular modeling of UGT1A1 (H55R, P152S and N212H) variants suggested a reduced activity of the enzyme. This study demonstrates that different variations present in the UGT1A1 gene and specifically, the H55R variation had a significant effect on bilirubin levels and could be genetic risk factors for hyperbilirubinemia.

Objective: The present study was undertaken to investigate the genotype and allele frequencies of the variants in the four bilirubin metabolism genes (UGT1A1, OATP2, HMOX1, and BLVRA) and their association with hyperbilirubinemia., Material and Methods: Genotyping of 17 genetic variants was performed in 115 adults with hyperbilirubinemia and 150 controls by PCR-RFLP, GeneScan analysis, and direct DNA sequencing., Results: Genetic polymorphisms of the UGT1A1 promoter, specifically the T-3279G phenobarbital-responsive enhancer module and (TA)7 dinucleotide repeat, as well as the intron and coding region variants of the OATP2, HMOX1, and BLVRA genes, were significantly higher among the cases than the controls. Further, nearly 82% of the cases showed the presence of significantly four or more variants as compared to 37% of the controls (P < 0.0001) and the mean total serum bilirubin levels also increased according to the number of variants co-expressed., Conclusions: This study demonstrates that polymorphisms in the bilirubin metabolism genes had a significant effect on bilirubin levels and could be genetic risk factors for hyperbilirubinemia., (© 2016 John Wiley & Sons Ltd/University College London.)