Integrated Genomic Analysis Identifies ANKRD36 Gene as a Novel and Common Biomarker of Disease Progression in Chronic Myeloid Leukemia

<b>Background:</b> Chronic myeloid leukemia (CML) is initiated in bone marrow due to chromosomal translocation t(9;22) leading to fusion oncogene BCR-ABL. Targeting BCR-ABL by tyrosine kinase inhibitors (TKIs) has changed fatal CML into an almost curable disease. Despite that, TKIs lose...

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Autores principales:	Zafar Iqbal, Muhammad Absar, Tanveer Akhtar, Aamer Aleem, Abid Jameel, Sulman Basit, Anhar Ullah, Sibtain Afzal, Khushnooda Ramzan, Mahmood Rasool, Sajjad Karim, Zeenat Mirza, Mudassar Iqbal, Maryam AlMajed, Buthinah AlShehab, Sarah AlMukhaylid, Nouf AlMutairi, Nawaf Al-anazi, Muhammad Farooq Sabar, Muhammad Arshad, Muhammad Asif, Masood Shammas, Amer Mahmood
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	CML disease progression common biomarker drug target ANRD36 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f81fb94a73054ad086543f8318509d8f
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spelling	oai:doaj.org-article:f81fb94a73054ad086543f8318509d8f2021-11-25T16:47:46ZIntegrated Genomic Analysis Identifies ANKRD36 Gene as a Novel and Common Biomarker of Disease Progression in Chronic Myeloid Leukemia10.3390/biology101111822079-7737https://doaj.org/article/f81fb94a73054ad086543f8318509d8f2021-11-01T00:00:00Zhttps://www.mdpi.com/2079-7737/10/11/1182https://doaj.org/toc/2079-7737<b>Background:</b> Chronic myeloid leukemia (CML) is initiated in bone marrow due to chromosomal translocation t(9;22) leading to fusion oncogene BCR-ABL. Targeting BCR-ABL by tyrosine kinase inhibitors (TKIs) has changed fatal CML into an almost curable disease. Despite that, TKIs lose their effectiveness due to disease progression. Unfortunately, the mechanism of CML progression is poorly understood and common biomarkers for CML progression are unavailable. This study was conducted to find novel biomarkers of CML progression by employing whole-exome sequencing (WES). <b>Materials and Methods</b>: WES of accelerated phase (AP) and blast crisis (BC) CML patients was carried out, with chronic-phase CML (CP-CML) patients as control. After DNA library preparation and exome enrichment, clustering and sequencing were carried out using Illumina platforms. Statistical analysis was carried out using SAS/STAT software version 9.4, and R package was employed to find mutations shared exclusively by all AP-/BC-CML patients. Confirmation of mutations was carried out using Sanger sequencing and protein structure modeling using I-TASSER followed by mutant generation and visualization using PyMOL. <b>Results</b>: Three novel genes (ANKRD36, ANKRD36B and PRSS3) were mutated exclusively in all AP-/BC-CML patients. Only ANKRD36 gene mutations (c.1183_1184 delGC and c.1187_1185 dupTT) were confirmed by Sanger sequencing. Protein modeling studies showed that mutations induce structural changes in ANKRD36 protein. <b>Conclusions</b>: Our studies show that ANKRD36 is a potential common biomarker and drug target of early CML progression. ANKRD36 is yet uncharacterized in humans. It has the highest expression in bone marrow, specifically myeloid cells. We recommend carrying out further studies to explore the role of ANKRD36 in the biology and progression of CML.Zafar IqbalMuhammad AbsarTanveer AkhtarAamer AleemAbid JameelSulman BasitAnhar UllahSibtain AfzalKhushnooda RamzanMahmood RasoolSajjad KarimZeenat MirzaMudassar IqbalMaryam AlMajedButhinah AlShehabSarah AlMukhaylidNouf AlMutairiNawaf Al-anaziMuhammad Farooq SabarMuhammad ArshadMuhammad AsifMasood ShammasAmer MahmoodMDPI AGarticleCMLdisease progressioncommon biomarkerdrug targetANRD36Biology (General)QH301-705.5ENBiology, Vol 10, Iss 1182, p 1182 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CML disease progression common biomarker drug target ANRD36 Biology (General) QH301-705.5
spellingShingle	CML disease progression common biomarker drug target ANRD36 Biology (General) QH301-705.5 Zafar Iqbal Muhammad Absar Tanveer Akhtar Aamer Aleem Abid Jameel Sulman Basit Anhar Ullah Sibtain Afzal Khushnooda Ramzan Mahmood Rasool Sajjad Karim Zeenat Mirza Mudassar Iqbal Maryam AlMajed Buthinah AlShehab Sarah AlMukhaylid Nouf AlMutairi Nawaf Al-anazi Muhammad Farooq Sabar Muhammad Arshad Muhammad Asif Masood Shammas Amer Mahmood Integrated Genomic Analysis Identifies ANKRD36 Gene as a Novel and Common Biomarker of Disease Progression in Chronic Myeloid Leukemia
description	<b>Background:</b> Chronic myeloid leukemia (CML) is initiated in bone marrow due to chromosomal translocation t(9;22) leading to fusion oncogene BCR-ABL. Targeting BCR-ABL by tyrosine kinase inhibitors (TKIs) has changed fatal CML into an almost curable disease. Despite that, TKIs lose their effectiveness due to disease progression. Unfortunately, the mechanism of CML progression is poorly understood and common biomarkers for CML progression are unavailable. This study was conducted to find novel biomarkers of CML progression by employing whole-exome sequencing (WES). <b>Materials and Methods</b>: WES of accelerated phase (AP) and blast crisis (BC) CML patients was carried out, with chronic-phase CML (CP-CML) patients as control. After DNA library preparation and exome enrichment, clustering and sequencing were carried out using Illumina platforms. Statistical analysis was carried out using SAS/STAT software version 9.4, and R package was employed to find mutations shared exclusively by all AP-/BC-CML patients. Confirmation of mutations was carried out using Sanger sequencing and protein structure modeling using I-TASSER followed by mutant generation and visualization using PyMOL. <b>Results</b>: Three novel genes (ANKRD36, ANKRD36B and PRSS3) were mutated exclusively in all AP-/BC-CML patients. Only ANKRD36 gene mutations (c.1183_1184 delGC and c.1187_1185 dupTT) were confirmed by Sanger sequencing. Protein modeling studies showed that mutations induce structural changes in ANKRD36 protein. <b>Conclusions</b>: Our studies show that ANKRD36 is a potential common biomarker and drug target of early CML progression. ANKRD36 is yet uncharacterized in humans. It has the highest expression in bone marrow, specifically myeloid cells. We recommend carrying out further studies to explore the role of ANKRD36 in the biology and progression of CML.
format	article
author	Zafar Iqbal Muhammad Absar Tanveer Akhtar Aamer Aleem Abid Jameel Sulman Basit Anhar Ullah Sibtain Afzal Khushnooda Ramzan Mahmood Rasool Sajjad Karim Zeenat Mirza Mudassar Iqbal Maryam AlMajed Buthinah AlShehab Sarah AlMukhaylid Nouf AlMutairi Nawaf Al-anazi Muhammad Farooq Sabar Muhammad Arshad Muhammad Asif Masood Shammas Amer Mahmood
author_facet	Zafar Iqbal Muhammad Absar Tanveer Akhtar Aamer Aleem Abid Jameel Sulman Basit Anhar Ullah Sibtain Afzal Khushnooda Ramzan Mahmood Rasool Sajjad Karim Zeenat Mirza Mudassar Iqbal Maryam AlMajed Buthinah AlShehab Sarah AlMukhaylid Nouf AlMutairi Nawaf Al-anazi Muhammad Farooq Sabar Muhammad Arshad Muhammad Asif Masood Shammas Amer Mahmood
author_sort	Zafar Iqbal
title	Integrated Genomic Analysis Identifies ANKRD36 Gene as a Novel and Common Biomarker of Disease Progression in Chronic Myeloid Leukemia
title_short	Integrated Genomic Analysis Identifies ANKRD36 Gene as a Novel and Common Biomarker of Disease Progression in Chronic Myeloid Leukemia
title_full	Integrated Genomic Analysis Identifies ANKRD36 Gene as a Novel and Common Biomarker of Disease Progression in Chronic Myeloid Leukemia
title_fullStr	Integrated Genomic Analysis Identifies ANKRD36 Gene as a Novel and Common Biomarker of Disease Progression in Chronic Myeloid Leukemia
title_full_unstemmed	Integrated Genomic Analysis Identifies ANKRD36 Gene as a Novel and Common Biomarker of Disease Progression in Chronic Myeloid Leukemia
title_sort	integrated genomic analysis identifies ankrd36 gene as a novel and common biomarker of disease progression in chronic myeloid leukemia
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f81fb94a73054ad086543f8318509d8f
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Integrated Genomic Analysis Identifies ANKRD36 Gene as a Novel and Common Biomarker of Disease Progression in Chronic Myeloid Leukemia

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