Evaluation the Level of Human P-glycoprotein in Acute Myeloid Leukemia and Response to Treatment

P-Glycoprotein Expression and Treatment Response in AML

Section: Research Paper
Issue
Vol. 48 No. 1 (2026): Volume 48 Issue 1
Pages
90-99

Keywords:

Acute myeloid leukemia, Human P-glycoprotein, Multi-drug resistance

Abstract

Background: Accurate diagnosis and classification of acute myeloid leukemia (AML) are essential for treatment decisions and assessment of prognosis. P-glycoprotein (P-gp) plays a key role in multidrug resistance and has been associated with adverse outcomes in AML.


Objective: is to evaluate the prognostic significance of serum P-gp levels in newly diagnosed AML patients, specifically regarding their association with initial treatment response. The study also explored correlations between P-gp levels and baseline laboratory parameters to identify potential biomarkers of multidrug resistance.


Methods: In this case-control observational study, P-gp levels were measured in 40 newly diagnosed AML patients admitted to Ibn-Sina and Al-Hadbaa hospitals before and after induction of chemotherapy in the period between January 2025 and June 2025. A total of 15 healthy individuals were included in this study as a control group.


Results: A significant statistical correlation was observed between P-gp level (pre-induction) and hemoglobin level, hematocrit and blood urea. Receiver operating characteristic analysis demonstrated a sensitivity of 75% and specificity of 64.3% at a cut-off value of 10.75 ng/mL indicating that a pre-induction P-gp level may serves as a predictor of poor treatment response and adverse patient prognosis. Furthermore, post-induction P-gp levels were significantly higher in patients with incomplete remission compared to those who achieved complete remission supporting the role of elevated P-gp as a biomarker of chemoresistance and adverse treatment outcome.


Conclusion: This study demonstrated that P-glycoprotein levels are higher in acute myeloid leukemia patients at the time of diagnosis than in the control group. Furthermore, higher levels of human P-glycoprotein may serve as a potential biomarker for poor treatment response. While these findings highlight the role of P-gp in chemoresistance, further evidence is needed to establish a definitive link between P-gp level and increased mortality.

References

  1. Bain BJ, Béné MC. Morphological and immunophenotypic clues to the WHO categories of acute myeloid leukaemia. Acta Haematol. 2019;141(4):232-244. Doi: https://doi.org/10.1159/000496097
  2. Estey E, Hasserjian RP, Döhner H. Distinguishing acute myeloid leukemia from myelodysplastic syndromes: a fixed blast percentage may no longer be optimal. Blood. 2022;139(3):323-332. Doi: https://doi.org/10.1182/blood.2021011304
  3. American Cancer Society. Cancer facts and figures 2024. Atlanta, GA: American Cancer Society; 2024.
  4. Guo Y, Wang W, Sun H. A systematic review and meta-analysis on the risk factors of acute myeloid leukemia. Transl Cancer Res. 2022;11(4):796-804. Doi: https://doi.org/10.21037/tcr-22-27.
  5. Shallis RM, Wang R, Davidoff A, Ma X, Zeidan AM, Hafez N, et al. Epidemiology of acute myeloid leukemia: recent progress and enduring challenges. Blood Rev. 2019;36:70–87. Doi: https://doi.org/10.1016/j.blre.2019.04.005.
  6. Vaidya FU, Sufiyan Chhipa A, Mishra V, Gupta VK, Rawat SG, Kumar A, et al. Molecular and cellular paradigms of multidrug resistance in cancer. Cancer Rep. 2022;5(12):e1291. Doi: https://doi.org/10.1002/cnr2.1291
  7. Thomas C, Tampé R. Structural and Mechanistic Principles of ABC Transporters. Annu Rev Biochem. 2022 Jun 21;91:605-636. Doi: https://doi.org/10.1146/annurev-biochem-011520-105201
  8. Wang JQ, Wu ZX, Yang Y, Teng QX, Li YD, Lei ZN, et al. ATP-binding cassette (ABC) transporters in cancer: a review of recent updates. J Evid Based Med. 2021;14(3):232–56. Doi: https://doi.org/10.1111/jebm.12434.
  9. Juliano RL, Ling V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta. 1976;455(1):152-16. Doi: https://doi.org/10.1016/0005-2736(76)90160-7.
  10. Ibrahim MAA, Abdeljawaad KAA, Jaragh-Alhadad LA, Oraby HF, Atia MAM, Alzahrani OR, et al. Potential drug candidates as P-glycoprotein inhibitors to reverse multidrug resistance in cancer: An in silico drug discovery study. J Biomol Struct Dyn. 2023;41:13977–13992. Doi: https://doi.org/10.1080/07391102.2023.2176360.
  11. Zhang H, Xu H, Ashby CR Jr, Assaraf YG, Chen ZS, Liu HM. Chemical molecular-based approach to overcome multidrug resistance in cancer by targeting P-glycoprotein (P-gp). Med Res Rev. 2021;41(2):525–555. Doi: https://doi.org/10.1002/med.21739
  12. Amawi H, Sim HM, Tiwari AK, Ambudkar SV, Shukla S. ABC transporter-mediated multidrug-resistant cancer. In: Drug Transporters in Drug Disposition, Effects and Toxicity. 1st ed. Springer; 2019. p. 549–80. Doi: https://doi.org/10.1007/978-981-13-7647-4_12
  13. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) Co-operative Group. Br J Haematol. 1976;33(4):451–458. Doi: https://doi.org/10.7326/0003-4819-103-3-460
  14. Bain BJ. Preparation and staining methods for blood and bone marrow films. In: Bain BJ, Bates I, Laffan MA. Dacie and Lewis Practical Haematology. 13th ed. Philadelphia: Elsevier; 2017.
  15. Assaraf YG, Brozovic A. The multi-factorial nature of clinical multidrug resistance in cancer. Drug Resist Updat. 2019;46:100645. Doi: https://doi.org/10.1016/j.drup.2019.100645
  16. Robey RW, Pluchino KM, Hall MD, Fojo AT, Bates SE, Gottesman MM. Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat Rev Cancer. 2018;18(7):452-464. Doi: https://doi.org/10.1038/s41568-018-0005-8.
  17. Duvivier L, Gerard L, Diaz A, Gillet JP. Linking ABC transporters to the hallmarks of cancer. Trends Cancer. 2024;10(2):124-134. Doi: https://doi.org/10.1016/j.trecan.2023.09.013
  18. Boscaro E, Urbino I, Catania FM, Arrigo G, Secreto C, Olivi M, et al. Modern risk stratification of acute myeloid leukemia in 2023: integrating established and emerging prognostic factors. Cancers (Basel). 2023;15(13):3512. Doi: https://doi.org/10.3390/cancers15133512.
  19. Al-Fatlawi HH, Musa RJ. Evaluation of CD96 and CD123 in CD34+ leukemic stem cells in acute myeloid leukemia patients and their relation to response to induction therapy. Iraqi J Hematol. 2016;5(2):161–166. Doi: https://doi.org/10.4103/2072-8069.198119.
  20. Tawfiq SA, Yassin AK, AlGetta HA, Hasan KM. Acute myeloblastic leukemia: Important clinical and epidemiological facts from Hiwa Hospital in Sulaimaniyah, Iraq. Iraqi J Hematol. 2019;8(2):69–73. Doi: https://doi.org/10.4103/ijh.ijh_11_19.
  21. Ahmed EQ, Al-Rubaie HA. Effect of remission induction therapy on the level of soluble urokinase plasminogen activator receptor in acute myeloid leukemia. Iraqi J Hematol. 2020;9(2):87-91. Doi: https://doi.org/10.4103/ijh.ijh_20_20
  22. Pouls RK, Shamoon RP, Muhammed NS. Clinical and haematological parameters in adult AML patients: a four year experience at Nanakaly Hospital for blood diseases. Zanco J Med Sci. 2012;16(3):199-203. Doi: https://doi.org/10.15218/zjms.2012.0035
  23. Husien SH, Al-Zubaidi AKAH. Survey of Adult Acute Myeloid Leukaemia Cases Reported in the Medical City in Baghdad through the Years 2005-2011. IAR Journal of Medical Sciences. 2021 Jan;2(1):1-5. Doi: https://doi.org/10.47310/iarjms.2021.v02i01.042
  24. Zayed RA, Eltaweel MA, Botros SK, Zaki MA. MN1 and PTEN gene expression in acute myeloid leukemia. Cancer Biomark. 2017;18(2):177–182. Doi: https://doi.org/10.3233/cbm-160235
  25. Short NJ, Rytting ME, Cortes JE. Acute myeloid leukaemia. Lancet. 2018;392(10147):593-606. Doi: https://doi.org/10.1016/s0140-6736(18)31041-9
  26. Saraymen B, Çimen B, Çetin İ, Köker M, Çetin A, Eser B, et al. Determination of P-glycoprotein expression by flow cytometry in hematological malignancies. Dicle Med J. 2016;43(1):33-38. Available from: https://dergipark.org.tr/en/pub/dicletip/article/237822
  27. Hirsch P, Tang R, Marzac C, Perrot JY, Fava F, Bernard C, et al. Prognostic impact of high ABC transporter activity in 111 adult acute myeloid leukemia patients with normal cytogenetics when compared to FLT3, NPM1, CEBPA and BAALC. Haematologica. 2012;97(2):241-245. Doi: https://doi.org/10.3324/haematol.2010.034447
  28. Álvarez-Carrasco P, Morales-Villamil F, Maldonado-Bernal C. P glycoprotein as a therapeutic target in hematological malignancies: a challenge to overcome. Int J Mol Sci. 2025;26(10):4701. Doi: https://doi.org/10.3390/ijms26104701
  29. Sourdeau E, Suner L, Memoli M, Genthon A, Feger F, Soret L, et al. Clinical and biological impact of ATP-binding cassette transporter activity in adult acute myeloid leukemia. Haematologica. 2023;108(1):61–68. Doi: https://doi.org/10.3324/haematol.2022.280676
  30. Del Poeta G, Venditti A, Aronica G, Stasi R, Cox MC, Buccisano F, et al. P-glycoprotein expression in de novo acute myeloid leukemia. Leuk Lymphoma. 1997;27(3–4):257–274. Doi: https://doi.org/10.3109/10428199709059682
  31. Indrasari YN, Hernaningsih Y, Aryati A, Bintoro SUY, Atika A, Hassan R, et al. Correlation between P-glycoprotein and CD34 expressions in leukemic cells from de novo acute myeloid leukemia. Biomol Health Sci J. 2024;7(2):81–87. Doi: https://doi.org/10.4103/bhsj.bhsj_54_23
  32. Perea G, Domingo A, Villamor N, Palacios C, Juncà J, Torres P, et al. Adverse prognostic impact of CD36 and CD2 expression in adult de novo acute myeloid leukemia patients. Leuk Res. 2005;29(10):1109–1116. Doi: https://doi.org/10.1016/j.leukres.2005.02.015
  33. Megías JE, Martínez-Cuadrón D, Herrero MJ, Moscardó F, Bosó V, Martínez-Cuadrón D, et al. Impact of transporter genes polymorphisms in standard induction of acute myeloid leukemia. Leuk Lymphoma. 2015;56(10):2931–2934. Doi: https://doi.org/10.1182/blood.V126.23.4842.4842
  34. Wuchter C, Leonid K, Ruppert V, Schrappe M, Büchner T, Schoch C, et al. Clinical significance of P-glycoprotein expression and function for response to induction chemotherapy, relapse rate and overall survival in acute leukemia. Haematologica. 2000;85(7):711-721. Available from https://pubmed.ncbi.nlm.nih.gov/10897123/
  35. Benderra Z, Faussat AM, Sayada L, Perrot JY, Chaoui D, Marie JP, et al. Breast cancer resistance protein and P-glycoprotein in 149 adult acute myeloid leukemias. Clin Cancer Res. 2004;10(23):7896–7902. Doi: https://doi.org/10.1158/1078-0432.ccr-04-0795
  36. Rodríguez-Macías G, Briz O, Cives-Losada C, Chillón MC, Martínez-Laperche C, Martínez-Arranz I, et al. Role of intracellular drug disposition in the response of acute myeloid leukemia to cytarabine and idarubicin induction chemotherapy. Cancers (Basel). 2023;15(12):3145. Doi: https://doi.org/10.3390/cancers15123145
  37. Kolesnikova MA, Sen'kova AV, Pospelova TI, Zenkova MA, et al. Effective prognostic model for therapy response prediction in acute myeloid leukemia patients. J Pers Med. 2023;13(8):1234. Doi: https://doi.org/10.3390/jpm13081234

Authors

Aya Mohammad Khudhur

Nineveh Health Directorate

Sadeel Osama Al-Shabkhoon

Nineveh Health Directorate

Identifiers

DOI: 10.33899/acmm.v48.i1.60365

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1.
Evaluation the Level of Human P-glycoprotein in Acute Myeloid Leukemia and Response to Treatment: P-Glycoprotein Expression and Treatment Response in AML. Ann. coll. Med. Mosul [Internet]. 2026 Jul. 1 [cited 2026 Jul. 18];48(1):90-9. Available from: https://mmed.uomosul.edu.iq/index.php/mmed/article/view/60365

How to Cite

1.
Evaluation the Level of Human P-glycoprotein in Acute Myeloid Leukemia and Response to Treatment: P-Glycoprotein Expression and Treatment Response in AML. Ann. coll. Med. Mosul [Internet]. 2026 Jul. 1 [cited 2026 Jul. 18];48(1):90-9. Available from: https://mmed.uomosul.edu.iq/index.php/mmed/article/view/60365