Expression of caspase-9 in bone marrow lymphoblasts in children with acute lymphoblastic leukemia

Anindita, Adecya Nararia; Ugrasena, I Dewa Gede; Hernaningsih, Yetty; Cahyadi, Andi

doi:10.48309/ecc.2024.422927.1720

Articles in Press

Document Type : Original Research Article

Authors

¹ Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia

² Departement of Child Health, Dr. Soetomo Public Academic Hospital, Surabaya, Indonesia

³ Departement of Clinical Pathology, Dr. Soetomo Public Academic Hospital, Surabaya, Indonesia

10.48309/ecc.2024.422927.1720

Abstract

Caspase-9 plays a critical role in mediating apoptosis through various intrinsic pathway triggers within the mitochondria. Failure to respond to apoptotic stimuli in Acute Lymphoblastic Leukemia (ALL) can lead to chemotherapy resistance related to deviations in the caspase pathway in lymphoblasts. This study aims to assess the caspase-9 expression both before and after the induction phase of chemotherapy in children with ALL and its association with several clinical parameters. This prospective study involved pediatric patients aged 1-18 years who were newly diagnosed with ALL and administered induction-phase chemotherapy following the 2018 Indonesian National Protocol for ALL treatment. The expression of caspase-9 was evaluated before and after the induction phase from bone marrow aspirate using flow cytometry. The variance in caspase-9 expression was examined using the Mann-Whitney U test, with p < 0.05 for a two-tailed test was considered statistically significant. Out of the 37 pediatric ALL cases, 17 met the specified criteria. The median expression of caspase-9 before chemotherapy in dead children was higher (p = 0.182). The median expression before chemotherapy increased after the induction phase of chemotherapy (p = 0.561). The caspase-9 expression was low in children with hepatomegaly and splenomegaly (p = 0.015, p = 0.009). Expression of caspase-9 was elevated after chemotherapy and higher in surviving children than in dead children. Caspase-9 expression before chemotherapy was low in children with hepatomegaly and splenomegaly.

Graphical Abstract

Keywords

Main Subjects

Cancer research

References

[1] G. Kapoor, N. Singh, Role of apoptotic markers in paediatric acute lymphoblastic leukaemia, Indian J Med Res, 2018, 147, 225-227. [Crossref], [Google Scholar], [Publisher]

[2] S. Abdelmabood, A.E. Fouda, F. Boujettif, A. Mansour, Treatment outcomes of children with acute lymphoblastic leukemia in a middle-income developing country: high mortalities, early relapses, and poor survival, Jornal de Pediatria, 2020, 96, 108–116. [Crossref], [Google Scholar], [Publisher]

[3] A. Cahyadi, E. Poespitaningtyas, D.K. Arumsari, M. C. S. Larasati, M. R. Andarsini, I. D.G. Ugrasena, Region variation of hematological mlignancies and
solid tumors in children in East Java, Asian J Heal Res, 2023, 2, 27−33. [Crossref], [Google Scholar], [Publisher]

[4] T. Liu, E. Raetz, P.J. Moos, S.L. Perkins, C.S. Bruggers, F. Smith, W.L. Carroll, Diversity of the apoptotic response to chemotherapy in childhood leukemia, Leukemia, 2002, 16, 223-232. [Crossref], [Google Scholar], [Publisher]

[5] A. Kakaje, M.M. Alhalabi, A. Ghareeb, B. Karam, B. Mansour, B. Zahra, O. Hamdan, Rates and trends of childhood acute lymphoblastic leukaemia: an epidemiology study, Sci Rep, 2020, 10, 6756. [Crossref], [Google Scholar], [Publisher]

[6] V.R. Lakshmidevi, D. Reeja, A.R. Rajan, B. Vinod, Advanced spectrum of imidazole derivatives in therapeutics: A review, Journal of Chemical Reviews, 2023, 5, 241-262. [Crossref], [Pdf], [Publisher]

[7] R. Kareem, N. Bulut, O. Kaygili, Hydroxyapatite biomaterials: A comprehensive review of their properties, structures, medical applications, and fabrication methods, Journal of Chemical Reviews, 2023, 6, 1-26. [Crossref], [Google Scholar], [Publisher]

[8] M. Hassan, H. Watari, A. AbuAlmaaty, Y. Ohba, N. Sakuragi, Apoptosis and molecular targeting therapy in cancer, Biomed Res Int., 2014, 2014, 150845. [Crossref], [Google Scholar], [Publisher]

[9] A. Muslihatin, M.R. Andarsini, A. Cahyadi, R.V. Prasetyo, I.D.G. Ugrasena, M.C.S. Larasanti, Renal function features in pediatric acute lymphoblastic leukemia during high-dose methotrexate chemotherapy, Bali Medical Journal, 2022, 11, 1587–1590. [Crossref], [Google Scholar], [Publisher]

[10] H.M. Al-Aamri, H.R. Irving, C. Bradley, T. Meehan-Andrews, Intrinsic and extrinsic apoptosis responses in leukaemia cells following daunorubicin treatment, BMC Cancer, 2021, 21, 438. [Google Scholar], [Publisher]

[11] M. Olsson, B. Zhivotovsky, Caspases and cancer, Cell Death & Differentiation, 2011, 18, 1441–1449. [Crossref], [Google Scholar], [Publisher]

[12] S. Trino, L. De Luca, I. Laurenzana, A. Caivano, L. Del Vecchio, G. Martinelli, P. Musto, P53-MDM2 pathway: evidences for a new targeted therapeutic approach in B-acute lymphoblastic leukemia, Front Pharmacol, 2016, 7, 491. [Crossref], [Google Scholar], [Publisher]

[13] C. Xiong, P. Li, Q. Luo, C.W. Phan, Q. Li, X. Jin, W. Huang, Induction of apoptosis in heLa cells by a novel peptide from fruiting bodies of morchella importuna via the mitochondrial apoptotic pathway, Evid Based Complement Alternat Med, 2021, 2021, 5563367. [Crossref], [Google Scholar], [Publisher]

[14] P. Li, L. Zhou, T. Zhao, X. Liu, P. Zhang, Y. Liu, X. Zheng, Q. Li, Caspase-9: structure, mechanisms, and clinical application, Oncotarget, 2017, 8, 23996-24008. [Crossref], [Google Scholar], [Publisher]

[15] P.M. Edathara, M. Gorre, S. Kagita, A. Cingeetham, S. Annamaneni, R. Digumarti, V. Satti, Influence of caspase-9 polymorphisms on the development of Chronic Myeloid Leukemia- A case-control study, Gene, 2019, 721S, 100002. [Crossref], [Google Scholar], [Publisher]

[16] N. Novia, N. Rosdiana, S. Supriatmo, Serum ferritin level in pediatric patients with acute lymphoblastic leukemia (ALL) in the early stage of diagnosis and remission phase, Bali Medical Journal, 2022, 11, 1598–1602. [Crossref], [Google Scholar], [Publisher]

[17] S. Chiaretti, G. Zini, R. Bassan. Diagnosis and Subclassification of Acute Lymphoblastic Leukemia, Mediterr J Hematol Infect Dis, 2014, 6, 1–12. [Crossref], [Google Scholar], [Publisher]

[18] N. Andria, A.G. Moelyo, M. Reza, Blood glucose level during induction phase chemotherapy in childhood acute lymphoblastic leukemia, Paediatrica Indonesiana, 2020, 60, 192-197. [Crossref], [Google Scholar], [Publisher]

[19] L. Holmes Jr, J. Hossain, M. Desvignes-Kendrick, F. Opara, Sex variability in pediatric leukemia survival: large cohort evidence, ISRN Oncol, 2012, 2012, 439070. [Crossref], [Google Scholar], [Publisher]

[20] H. Butt, A. Khalid, M. Yaqoob, Polymorphismm of BCL2 gene in acute lymphoblastic leukemia pastients in Pakistan and screening of phytochemicals to overcome its expression, Bio Med (Aligarh), 2017, 10, 1000424. [Crossref], [Google Scholar], [Publisher]

[21] E.J. Salim, K. Ariawati, I.W. Gustawan, I.G.A.T. Windiani, E. Gunawijaya, I.N.B. Hartawan, Diagnostic accuracy of bone marrow morphology to determine remission in acute lymphoblastic leukemia children: the role of minimal residual disease, Bali Medical Journal, 2020, 9, 366–370. [Crossref], [Google Scholar], [Publisher]

[22] J.C. Jaime-Pérez, M.A. Pinzón-Uresti, R.A. Jiménez-Castillo, J.E. Colunga-Pedraza, Ó. González-Llano, D. Gómez-Almaguer, Relapse of childhood acute lymphoblastic leukemia and outcomes at a reference center in Latin America: organomegaly at diagnosis is a significant clinical predictor, Hematology, 2018, 23, 1-9. [Crossref], [Google Scholar], [Publisher]

[23] K.J. Endrawati, N.N Mahartini, S. Herawati, A T-acute lymphoblastic leukemia in children with CD 117 expression: a case report, Bali Medical Journal, 2019, 8, 577–582. [Crossref], [Google Scholar], [Publisher]

[24] Z. Madadi, S. Akbari-Birgani, P.D. Monfared, S. Mohammadi, The non-apoptotic role of caspase-9 promotes differentiation in leukemic cells, Biochim Biophys Acta Mol Cell Res, 2019, 1866, 118524. [Crossref], [Google Scholar], [Publisher]

[25] R.T. Clarke, A. Van den Bruel, C. Bankhead, C.D. Mitchell, B. Phillips, M.J. Thompson, Clinical presentation of childhood leukaemia: a systematic review and meta-analysis, Arch Dis Child, 2016, 101, 894-901. [Crossref], [Google Scholar], [Publisher]

[26] M.J. Hossain, L. Xie, S.M. McCahan, Characterization of pediatric acute lymphoblastic leukemia survival patterns by age at diagnosis, J Cancer Epidemiol, 2014, 2014, 865979. [Crossref], [Google Scholar], [Publisher]

[27] K. Kustiah, Y. Hernaningsih, Y, Acute Lymphoblastic Leukemia (B-ALL) with co-expression of CD33 and CD13, Bali Medical Journal, 2023, 12. [Crossref], [Google Scholar], [Publisher]

[28] R. Kanagal-Shamanna, P. Jain, K. Takahashi, N.J .Short, G. Tang, G.C. Issa, F. Ravandi, G. Garcia-Manero, C.C. Yin, R. Luthra, K.P. Patel, J.D. Khoury, G. Montalban-Bravo, K. Sasaki, T.M. Kadia, G. Borthakur, M. Konopleva, N. Jain, R. Garris, S. Pierce, W. Wierda, Z. Estrov, J. Cortes, S. O’Brien, H.M. Kantarijan, E. Jabbour, TP53 mutation does not confer a poor outcome in adult patients with acute lymphoblastic leukemia who are treated with frontline hyper-CVAD-based regimens, Cancer, 2017, 123, 3717-3724. [Crossref], [Google Scholar], [Publisher]

[29] K.R. Schultz, D.J. Pullen, H.N. Sather, J.J. Shuster, M. Devidas, M.J. Borowitz, A.J. Carroll, N.A. Heerema, J.E. Rubnitz, M.L. Loh, E.A. Raetz, N.J. Winick, S.P. Hunger, W.L. Carroll, P.S. Gaynon, B.M. Camitta, Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children's Cancer Group (CCG), Blood, 2007, 109, 926-35. [Crossref], [Google Scholar], [Publisher]

[30] M.B. Uddin, M. Hoque, M. Ali, A. Islam, R. Miah, Abandonment and outcome of induction chemotherapy in childhood acute lymphoblastic leukemia, Research In Cancer and Tumor, 2021, 9, 8-14. [Crossref], [Google Scholar], [Publisher]

[31] W.K. Abdullah, F.A. Maha, Caspase 9 gene expression and caspase 9 proten in chronic myeloid leukemia in IRAQ, Iraqi Journal of Agricultural Sciences, 2022, 53, 994-1002. [Google Scholar], [Publisher]

[32] J. Dörrie, H. Gerauer, Y. Wachter, S.J Zunino, Resveratrol induces extensive apoptosis by depolarizing mitochondrial membranes and activating caspase-9 in acute lymphoblastic leukemia cells, Cancer Res, 2001, 61, 4731-4739. [Google Scholar], [Publisher]

[33] K. Janssen, S. Pohlmann, R.U. Janicke, K. Schulze-Osthoff, U. Fischer, Apaf-1 and caspase-9 deficiency prevents apoptosis in a Bax-controlled pathway and promotes clonogenic survival during paclitaxel treatment, Blood, 2007, 110, 3662–72. [Crossref], [Google Scholar], [Publisher]

[34] M.R. Nasution, P.C. Tampubolon, I.S. Nasution, Absolute neutrophil count as predictor hematopoietic recovery in acute lymphoblastic leukemia in remission induction phase chemotherapy, Bali Medical Journal, 2022, 11, 471–475. [Google Scholar], [Publisher]

[35] I. Herr, E. Ucur, K. Herzer, S. Okouoyo, R. Ridder, P.H. Krammer, M.V.K. Doeberitz, K.M. Debatin, Glucocorticoid cotreatment induces apoptosis resistance toward cancer therapy in carcinomas, Cancer Res, 2003, 63, 3112-3120. [Google Scholar], [Publisher]

[36] W. Xu, S. Jiang, Y. Xu, B. Chen, Y. Li, F. Zong, W. Zhao, J. Wu, A meta-analysis of caspase 9 polymorphisms in promoter and exon sequence on cancer Susceptibility, PLoS One, 2012, 7, 37443. [Crossref], [Google Scholar], [Publisher]

[37] S. Sharifi, J. Barar, M.S. Hejazi, N. Samadi, Doxorubicin changes Bax/Bcl-xl ratio, caspase-8 and caspase-9 in breast cancer cells, Adv Pharm Bull, 2015, 5, 351-359. [Crossref], [Google Scholar], [Publisher]

[38] S.M. Warli, D.R.L. Ringoringo, B. Sihombing, G.P. Siregar, F.F. Prapiska, The role of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in determining the prognosis of patients with testicular cancer, Bali Medical Journal, 2022, 11, 373–376. [Crossref], [Google Scholar], [Publisher]

[39] S. McComb, P.K. Chan, A. Guinot, H. Hartmannsdottir, S. Jenni, M.P. Dobay, J.P. Bourquin, B.C. Bornhauser, Efficient apoptosis requires feedback amplification of upstream apoptotic signals by effector caspase-3 or -7, Sci Adv, 2019, 5, 9433.[Crossref], [Google Scholar], [Publisher]

Eurasian Chemical Communications

Expression of caspase-9 in bone marrow lymphoblasts in children with acute lymphoblastic leukemia

References

References

Articles in Press, Accepted Manuscript
Available Online from 09 December 2023

Expression of caspase-9 in bone marrow lymphoblasts in children with acute lymphoblastic leukemia

References

References

Articles in Press, Accepted Manuscript Available Online from 09 December 2023

Articles in Press, Accepted Manuscript
Available Online from 09 December 2023