{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:58:24Z","timestamp":1790794704629,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T00:00:00Z","timestamp":1653264000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004530","name":"Universiti Putra Malaysia","doi-asserted-by":"publisher","award":["04-01-11-1333RU"],"award-info":[{"award-number":["04-01-11-1333RU"]}],"id":[{"id":"10.13039\/501100004530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004530","name":"Universiti Putra Malaysia","doi-asserted-by":"publisher","award":["02-01-04-SF008"],"award-info":[{"award-number":["02-01-04-SF008"]}],"id":[{"id":"10.13039\/501100004530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003200","name":"Kementerian Sains, Teknologi dan Inovasi","doi-asserted-by":"publisher","award":["04-01-11-1333RU"],"award-info":[{"award-number":["04-01-11-1333RU"]}],"id":[{"id":"10.13039\/501100003200","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003200","name":"Kementerian Sains, Teknologi dan Inovasi","doi-asserted-by":"publisher","award":["02-01-04-SF008"],"award-info":[{"award-number":["02-01-04-SF008"]}],"id":[{"id":"10.13039\/501100003200","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004726","name":"Ministry of Health","doi-asserted-by":"publisher","award":["04-01-11-1333RU"],"award-info":[{"award-number":["04-01-11-1333RU"]}],"id":[{"id":"10.13039\/501100004726","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004726","name":"Ministry of Health","doi-asserted-by":"publisher","award":["02-01-04-SF008"],"award-info":[{"award-number":["02-01-04-SF008"]}],"id":[{"id":"10.13039\/501100004726","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2022,5,23]]},"abstract":"<jats:p>Cancer immunotherapies are preferred over conventional treatments which are highly cytotoxic to normal cells. Focus has been on T cells but natural killer (NK) cells have equal potential. Concepts in cancer control and influence of sex require further investigation to improve successful mobilization of immune cells in cancer patients. Acute lymphoblastic leukemia (ALL) is a hematological malignancy mainly of B cell (B-ALL) and T cell (T-ALL) subtypes. Influence of ALL on NK cell is still unclear. Targeted next-generation sequencing was conducted on 62 activating\/inhibitory receptors, ligands, effector, and exhaustion molecules on T-ALL (6 males) and normal controls (NC) (4 males and 4 females). Quantitative PCR (q-PCR) further investigated copy number variation (CNV), methylation index (MI), and mRNA expression of significant genes in T-ALL (14 males), NC (12 males and 12 females), and B-ALL samples (<jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:mi>N<\/a:mi>\n                        <a:mo>=<\/a:mo>\n                        <a:mn>12<\/a:mn>\n                     <\/a:math>\n                  <\/jats:inline-formula> males and 12 females). Bioinformatics revealed unique variants particularly rs2253849 (T&gt;C) in KLRC1 and rs1141715 (A&gt;G) in KLRC2 only among T-ALL (allele frequency 0.8-1.0). Gene amplification was highest in female B-ALL compared to male B-ALL (KLRC2, KLRC4, and NCR3, <jats:inline-formula>\n                     <c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <c:mi>p<\/c:mi>\n                        <c:mo>&lt;<\/c:mo>\n                        <c:mn>0.05<\/c:mn>\n                     <\/c:math>\n                  <\/jats:inline-formula>) and lowest in male T-ALL cumulating in deletion of KLRD1 and CD69. MI was higher in male ALL of both subtypes compared to normal (KIR2DL1-2 and 4 and KIR2DS2 and 4, <jats:inline-formula>\n                     <e:math xmlns:e=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\">\n                        <e:mi>p<\/e:mi>\n                        <e:mo>&lt;<\/e:mo>\n                        <e:mn>0.05<\/e:mn>\n                     <\/e:math>\n                  <\/jats:inline-formula>) as well as to female B-ALL (KIR3DL2 and KIR2DS2, <jats:inline-formula>\n                     <g:math xmlns:g=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\">\n                        <g:mi>p<\/g:mi>\n                        <g:mo>&lt;<\/g:mo>\n                        <g:mn>0.05<\/g:mn>\n                     <\/g:math>\n                  <\/jats:inline-formula>). mRNA expressions were low. Thus, ALL subtypes potentially regulated NK cell suppression by different mechanisms which should be considered in future immunotherapies for ALL.<\/jats:p>","DOI":"10.1155\/2022\/7972039","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T18:35:19Z","timestamp":1653330919000},"page":"1-13","source":"Crossref","is-referenced-by-count":7,"title":["Differential Regulation of NK Cell Receptors in Acute Lymphoblastic Leukemia"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6789-4772","authenticated-orcid":true,"given":"Le Jie","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pathology, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8506-2240","authenticated-orcid":true,"given":"Norfarazieda","family":"Hassan","sequence":"additional","affiliation":[{"name":"UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia"},{"name":"Regenerative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, 13200 Kepala Batas, Penang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6231-7415","authenticated-orcid":true,"given":"Siti Zuleha","family":"Idris","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0505-7554","authenticated-orcid":true,"given":"Suresh Kumar","family":"Subbiah","sequence":"additional","affiliation":[{"name":"UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400 UPM, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2189-327X","authenticated-orcid":true,"given":"Heng Fong","family":"Seow","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0084-6025","authenticated-orcid":true,"given":"Norhafizah","family":"Mohtaruddin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine & Health Sciences, 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