High STAT5A Expression is Associated with Major Molecular Response Achievement Failure of Chronic Phase Chronic Myeloid Leukemia Patients Receiving Hydroxyurea before Imatinib: A Cross-sectional Study

Open Access Macedonian Journal of Medical Sciences

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Title High STAT5A Expression is Associated with Major Molecular Response Achievement Failure of Chronic Phase Chronic Myeloid Leukemia Patients Receiving Hydroxyurea before Imatinib: A Cross-sectional Study
 
Creator Rinaldi, Ikhwan
Putri, Anastasia
Louisa, Melva
Koesnoe, Sukamto
 
Subject Imatinib
Breakpoint cluster region-ABL
STAT5A
STAT5B
Chronic myeloid leukemia
 
Description BACKGROUND: STAT5 is a transcriptional factor which when highly expressed in chronic myeloid leukemia (CML) cells stimulate proliferation and mediate resistance from tyrosine kinase inhibitors, resulting in major molecular response (MMR) failure. STAT5 has two isoforms, STAT5A and STAT5B. However, prolonged use of imatinib appears to only upregulate STAT5A pathway. In addition, the resistance conferred by STAT5A does not extend to other drugs such as hydroxyurea. Hence, STAT5A and STAT5B might have different functions in CML cells.


AIM: The objective of the study was to determine the association of STAT5A and STAT5B expression with MMR failure in CML patients.


METHODS: This was a cross-sectional study of CML patients in chronic phase with age ≥ 18 years old, receiving IM therapy ≥ 12 months, and previously given hydroxyurea. MMR status was evaluated and patients were categorized as achieved or failed to achieve MMR. Expression levels of STAT5A and STAT5B were conducted using RT-PCR methods. Associations between STAT5A expression, STAT5B expression, hydroxyurea duration, and imatinib duration with MMR achievement were calculated using logistic regression.


RESULTS: A total of 118 patients were analyzed; 71.1% failed to achieve MMR. Multivariate logistic regression analysis showed statistically significant association between high STAT5A expression (odds ratio [OR]: 3.852; 95% confidence interval [CI]: 1.420–10.452; p = 0.008), STAT5A/STAT5B interaction (OR: 0.150; 95% CI: 0.038–0.593; p = 0.007), longer hydroxyurea administration (OR: 3.882; 95% CI: 1.023–14.733; p = 0.046), and shorter imatinib administration (OR: 0.333; 95% CI: 0.132–0.840; p = 0.020) with MMR achievement failure. After adjusting STAT5A expression with STAT5A/STAT5B interaction, high STAT5A expression independently increased the likelihood of MMR achievement failure only in high expression STAT5B patients (OR: 3.852; 95% CI: 1.420–10.452; p = 0.008).

CONCLUSION: High STAT5A expression which is induced by high STAT5B is associated with MMR achievement failure of chronic phase CML patients who received hydroxyurea before imatinib. Longer duration of hydroxyurea and shorter duration of IM confound of STAT5A expression to MMR achievement failure.
 
Publisher Scientific Foundation SPIROSKI, Skopje, Republic of Macedonia
 
Date 2021-09-29
 
Type info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
 
Format application/pdf
 
Identifier https://oamjms.eu/index.php/mjms/article/view/6911
10.3889/oamjms.2021.6911
 
Source Open Access Macedonian Journal of Medical Sciences; Vol. 9 No. B (2021): B - Clinical Sciences; 1160-1167
1857-9655
 
Language eng
 
Relation https://oamjms.eu/index.php/mjms/article/view/6911/6171
 
Rights Copyright (c) 2020 Ikhwan Rinaldi, Anastasia Putri, Melva Louisa, Sukamto Koesnoe (Author)
http://creativecommons.org/licenses/by-nc/4.0
 

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