NK cell defects: implication in acute myeloid leukemia.

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.

Identification of the novel HLA-A*01:01:01:111 allele in two individuals from Uttar Pradesh, India.

The novel HLA-A*01:01:01:111 allele was detected during routine HLA typing.

Identification of the HLA-B*40:01:02:59 and -C*05:01:73 alleles in individuals from the northern regions of India.

The novel HLA-B*40:01:02:59 and HLA-C*05:01:73 alleles were detected during the routine HLA typing process.

Identification of the novel HLA-C*12:02:47 allele in an individual from Maharashtra, India.

The novel HLA-C*12:02:47 allele was detected during routine HLA typing.

Identification of the novel HLA allele, HLA-B*37:01:01:19, in an individual from northern India.

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.

Identification of HLA-C*03:599 novel allele variant in two South Indian individuals in a Brahmin family.

The novel allele HLA-C*03:599 as compared with HLA-C*03:04:01:02 displays polymorphism at position; gDNA 1618 (G>T).

Detection of novel HLA-A*33:03:62, HLA-B*52:01:01:25 alleles and confirmation of HLA-A*02:01:209.

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.

Identification of the novel HLA-DQA1*01:01:01:11 and -DQA1*01:03:01:13 alleles in individuals from India.

The novel alleles HLA-DQA1*01:01:01:11 and -DQA1*01:03:01:13 were detected during the routine HLA typing process.

Identification of the novel HLA-DPA1*01:03:01:64 allele in an individual from Uttar Pradesh, India.

The novel HLA-DPA1*01:03:01:64 allele was detected during routine HLA typing.

Characterization of the novel HLA allele, HLA-C*07:04:01:19, in an individual from Maharashtra, India.

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.

Identification of the novel HLA-C*07:02:01:184 allele in an Indian individual from a Kshatriya family.

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).

The novel HLA-B*40:02:01:39 allele in an individual from a Kshatriya family in North India.

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.

Characterization of the novel HLA-B*58:01:01:19 allele by next-generation sequencing.

The novel HLA-B*58:01:01:19 allele was characterized using next generation sequencing technology.

Identification of the novel HLA-DQB1*06:01:01:04 allele in an individual from Western India.

The novel HLA-DQB1*06:01:01:04 allele was detected during routine HLA typing.

The novel HLA-B*52:01:01:23 allele in an individual from Uttar Pradesh, North India.

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.

Identification of the novel allele, HLA-C*06:02:38:02, in a Gujarati individual from India.

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.

Identification of the novel allele, HLA-A*02:11:01:06, in two North Indian individuals in a Kshatriya family.

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).

Identification of the novel HLA allele, HLA-A*11:01:01:86, in an individual from north India.

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).

Identification of the novel HLA-A *24:02:01:136 allele in a Northern Indian individual from a Muslim family.

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).

Identification of the novel HLA-DQA1*01:01:01:10 allele in an individual from Orissa, India.

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.