Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Typ-2-Diabetes und Adipositas Klimawandel und Gesundheit Neues aus dem Markt Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende Patientenratgeber
Erweiterte Suche
Anmelden
nach oben
Clinical and Translational Oncology
Erschienen in:

05.01.2022 | Research Article

Negative value of CD10−/CD34− immunophenotype in pediatric leukemia and development of a related cell line model for investigating drug resistance

verfasst von: N. Aberuyi, S. Rahgozar

Erschienen in: Clinical and Translational Oncology | Ausgabe 6/2022

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Appropriate sub-classification of leukemia according to the immunophenotypic characteristics of the malignant cells may improve therapeutic strategies. The aim of this study was to investigate the prognostic value of CD10/CD34 surface markers in pediatric acute lymphoblastic leukemia (pALL).

Patients and methods

A retrospective cohort study was performed in 79 children with ALL. Possible correlation between leukemia prognosis and CD10 CD34 immunophenotype was assessed using Kaplan–Meier and Cox regression analyses. A CD10- CD34- pre-B-ALL cell line was generated from a patient with resistant ALL. RN95 was characterized using light microscopy, immunophenotyping, karyotyping, and Western blotting. Drug sensitivity and resistant genes’ expression profile were assessed using MTT and RT-PCR assays.

Results

Kaplan–Meier analysis showed negative correlation between CD10/CD34 double negativity and patients’ 2- and 5-year disease-free survival (DFS). Multivariate analysis indicated that the absence of CD10 and CD34 expression in the ALL patients was an independent negative prognostic marker for 2- and 5-year DFS. A novel cell line model, RN95, was developed with similar immunophenotype from a primary relapsed sample. Cells showed p53 positive functionality and demonstrated partial sensitivity to Vincristine, but complete resistance to Cytarabine. Overexpression of ABCB1, ABCA2, and ABCA3 was detected.

Conclusion

In the current study, simultaneous absence of CD10 and CD34 cell surface markers was introduced as an unfavorable prognostic factor in pediatric B-ALL. Moreover, a special cell line was established to help delineation of novel therapeutics for B-ALL drug resistance.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Kachalaki S, Ebrahimi M, Khosroshahi LM, Mohammadinejad S, Baradaran B. Cancer chemoresistance; biochemical and molecular aspects: a brief overview. Eur J Pharm Sci. 2016;89:20–30.CrossRef
2.
Wang X, Zhang H, Chen X. Drug resistance and combating drug resistance in cancer. Cancer Drug Resist. 2019;2:141–60.PubMedPubMedCentral
3.
Aberuyi N, Rahgozar S, Moafi A. The role of ATP-binding cassette transporter A2 in childhood acute lymphoblastic leukemia multidrug resistance. Iran J Pediatr Hematol Oncol. 2014;4(3):118.
4.
Aberuyi N, Rahgozar S, Ghodousi ES, Ghaedi K. Drug resistance biomarkers and their clinical applications in childhood acute lymphoblastic leukemia. Front Oncol. 2019;9:1496.CrossRef
5.
Ghodousi ES, Aberuyi N, Rahgozar S. Simultaneous changes in expression levels of BAALC and miR-326: a novel prognostic biomarker for childhood ALL. Jpn J Clin Oncol. 2020;50:671–8.CrossRef
6.
Zhang J, Gu Y, Chen B. Mechanisms of drug resistance in acute myeloid leukemia. Onco Targets Ther. 2019;12:1937.CrossRef
7.
Chen KG, Duran GE, Mogul MJ, Wang YC, Ross KL, Jaffrézou J-P, et al. Genomic stability at the coding regions of the multidrug transporter gene ABCB1: insights into the development of alternative drug resistance mechanisms in human leukemia cells. Cancer Drug Resist. 2020;3(4):959–79.PubMedPubMedCentral
8.
Van Dongen J, Orfao A. EuroFlow: resetting leukemia and lymphoma immunophenotyping. Basis for companion diagnostics and personalized medicine. Leukemia. 2012;26(9):1899–907.CrossRef
9.
Kruse A, Abdel-Azim N, Kim HN, Ruan Y, Phan V, Ogana H, et al. Minimal residual disease detection in acute lymphoblastic leukemia. Int J Mol Sci. 2020;21(3):1054.CrossRef
10.
Sharma M, Sachdeva MUS, Varma N, Varma S, Marwaha R. Characterization of immunophenotypic aberrancies in adult and childhood acute lymphoblastic leukemia: a study from Northern India. J Cancer Res Ther. 2016;12(2):620.CrossRef
11.
Shahni A, Saud M, Siddiqui S, Mukry SN. Expression of aberrant antigens in hematological malignancies: a single center experience. Pak J Med Sci. 2018;34(2):457.CrossRef
12.
Dakka N, Bellaoui H, Bouzid N, Khattab M, Bakri Y, Benjouad A. CD10 and CD34 expression in childhood acute lymphoblastic leukemia in Morocco: clinical relevance and outcome. Pediatr Hematol Oncol. 2009;26(4):216–31.CrossRef
13.
Supriyadi E, Veerman A, Sutaryo S, van de Ven P, Cloos J. Detection of CD10, CD34 and their combined expression on childhood acute lymphoblastic leukemia and the association with clinical outcome in Indonesia. J Cancer Ther Res. 2012;1:1–10.CrossRef
14.
Pui C-H, Hancock ML, Head DR, Rivera GK, Look AT, Sandlund JT, et al. Clinical significance of CD34 expression in childhood acute lymphoblastic leukemia. Blood. 1993;82(3):889–94.CrossRef
15.
Hann I, Richards S, Eden O, Hill F. Analysis of the immunophenotype of children treated on the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia trial XI (MRC UKALLXI). Leukemia. 1998;12(8):1249–55.CrossRef
16.
Jaafar FH, Kadhom AE. Expression of CD45, CD34, CD10, and human leukocyte antigen-DR in acute lymphoblastic leukemia. Iraq J Hematol. 2018;7(1):14–9.
17.
18.
Gao C, Liu S-G, Yue Z-X, Liu Y, Liang J, Li J, et al. Clinical-biological characteristics and treatment outcomes of pediatric pro-B ALL patients enrolled in BCH-2003 and CCLG-2008 protocol: a study of 121 Chinese children. Cancer Cell Int. 2019;19(1):293.CrossRef
19.
Rivera-Luna R, Cardenas-Cardos R, Leal-Leal C, Navarro-Alegría I, Meza-Coria C, Gómez-Martínez R, et al. B-lineage acute lymphoblastic leukemia of childhood. An institutional experience. Arch Med Res. 1997;28(2):233–9.PubMed
20.
Consolini R, Legitimo A, Rondelli R, Guguelmi C, Barisone E, Lippi A, et al. Clinical relevance of CD10 expression in childhood ALL. The Italian Association for Pediatric Hematology and Oncology (AIEOP). Haematologica. 1998;83(11):967–73.PubMed
21.
Thomas X, Archimbaud E, Charrin C, Magaud J, Fiere D. CD34 expression is associated with major adverse prognostic factors in adult acute lymphoblastic leukemia. Leukemia. 1995;9(2):249–53.PubMed
22.
Rahimi BS, Rahgozar S, Mohammadi M. Ginger extract has anti-leukemia and anti-drug resistant effects on malignant cells. J Cancer Res Clin Oncol. 2019;145:1987–98.CrossRef
23.
Jandu H, Aluzaite K, Fogh L, Thrane SW, Noer JB, Proszek J, et al. Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines. BMC Cancer. 2016;16(1):34.CrossRef
24.
Barch MJ, Knutsen T, Spurbeck JL. The AGT cytogenetics laboratory manual. 3rd ed. Philadelphia: Lippincott-Raven; 1997.
25.
Kumar D, Panigrahi M, Saikia K, Kapoor G, Mehta A. Molecular analysis of childhood B-acute lymphoblastic leukemia: identification and prognosis of rare breakpoints. Mol Biol. 2015;49(6):843–7.CrossRef
26.
Franklin M, Gentles L, Matheson E, Bown N, Cross P, Ralte A, et al. Characterization and drug sensitivity of a novel human ovarian clear cell carcinoma cell line genomically and phenotypically similar to the original tumor. Cancer Med. 2018;7(9):4744–54.CrossRef
27.
Aberuyi N, Rahgozar S, Pourabutaleb E, Ghaedi K. Selective dysregulation of ABC transporters in methotrexate-resistant leukemia T-cells can confer cross-resistance to cytarabine, vincristine and dexamethasone, but not doxorubicin. Curr Res Transl Med. 2020;69:103269.CrossRef
28.
Aberuyi N, Rahgozar S, Pourabutaleb E, Ghaedi K. Selective dysregulation of ABC transporters in methotrexate-resistant leukemia T-cells can confer cross-resistance to cytarabine, vincristine and dexamethasone, but not doxorubicin. Curr Res Transl Med. 2021;69(1):103269.CrossRef
29.
Rahgozar S, Moafi A, Abedi M, Entezar-E-Ghaem M, Moshtaghian J, Ghaedi K, et al. mRNA expression profile of multidrug-resistant genes in acute lymphoblastic leukemia of children, a prognostic value for ABCA3 and ABCA2. Cancer Biol Ther. 2014;15(1):35–41.CrossRef
30.
DiGiuseppe JA, Cardinali JL. Immunophenotyping of acute lymphoblastic leukemia. In: Immunophenotyping. Berlin: Springer; 2019. p. 297–310.CrossRef
31.
Chiaretti S, Zini G, Bassan R. Diagnosis and subclassification of acute lymphoblastic leukemia. Mediterr J Hematol Infect Dis. 2014;6(1):e2014073.CrossRef
32.
Irving J. Diagnostic flow cytometry and immunophenotypic classification. Childhood acute lymphoblastic leukemia. Berlin: Springer; 2017. p. 49–59.CrossRef
33.
Sidhom I, Shaaban K, Soliman S, Ezzat S, El-Anwar W, Hamdy N, et al. Clinical significance of immunophenotypic markers in pediatric T-cell acute lymphoblastic leukemia. J Egypt Natl Canc Inst. 2008;20(2):111–20.PubMed
34.
Bene M, Castoldi G, Knapp W, Ludwig W-D, Matutes E, Orfao A, et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia. 1995;9(10):1783–6.PubMed
35.
Ross J, Rashkovan M, Fraszczak J, Joly-Beauparlant C, Vadnais C, Winkler R, et al. Deletion of the Miz-1 POZ domain increases efficacy of cytarabine treatment in T-and B-ALL/lymphoma mouse models. Can Res. 2019;79(16):4184–95.CrossRef
36.
Atra A, Gerrard M, Hobson R, Imeson J, Ashley S, Pinkerton C. Improved cure rate in children with B-cell acute lymphoblastic leukaemia (B-ALL) and stage IV B-cell non-Hodgkin’s lymphoma (B-NHL)-results of the UKCCSG 9003 protocol. Br J Cancer. 1998;77(12):2281–5.CrossRef
37.
Galmarini CM, Warren G, Senanayake MT, Vinogradov SV. Efficient overcoming of drug resistance to anticancer nucleoside analogs by nanodelivery of active phosphorylated drugs. Int J Pharm. 2010;395(1–2):281–9.CrossRef
38.
Jordheim LP, Durantel D, Zoulim F, Dumontet C. Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases. Nat Rev Drug Discov. 2013;12(6):447–64.CrossRef
39.
Aberuyi N, Rahgozar S, Dehaghi ZK, Moafi A, Masotti A, Paolini A. The translational expression of ABCA2 and ABCA3 is a strong prognostic biomarker for multidrug resistance in pediatric acute lymphoblastic leukemia. Onco Targets Ther. 2017;10:3373.CrossRef
Metadaten
Titel
Negative value of CD10−/CD34− immunophenotype in pediatric leukemia and development of a related cell line model for investigating drug resistance
verfasst von
N. Aberuyi
S. Rahgozar
Publikationsdatum
05.01.2022
Verlag
Springer International Publishing
Erschienen in
Clinical and Translational Oncology / Ausgabe 6/2022
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-021-02755-x

Weitere Artikel der Ausgabe 6/2022

Reply to “Letter to the editor regarding ‘Stereotactic radiosurgery for bone metastases in oligometastatic prostate cancer patients: DESTROY-2 clinical trial subanalysis’”

  • Correspondence

Pediatric medulloblastoma express immune checkpoint B7-H3

  • Open Access
  • Brief Research Article

Current status and future perspectives in HER2 positive advanced gastric cancer

  • Review Article

MicroRNA-4463 facilitates the development of colon cancer by suppression of the expression of PPP1R12B

  • Research Article

Circulating myeloid-derived suppressors cells correlate with clinicopathological characteristics and outcomes undergoing neoadjuvant chemoimmunotherapy in non-small cell lung cancer

  • Research Article

The inhibitory effect of LINC00261 upregulation on the pancreatic cancer EMT process is mediated by KLF13 via the mTOR signaling pathway

  • Research Article

Neu im Fachgebiet Onkologie

Welche Krebserkrankungen bei Zöliakie häufiger auftreten

Eine große Kohortenstudie hat den Zusammenhang zwischen Zöliakie und gastrointestinalen Krebserkrankungen und inflammatorischen Krankheiten untersucht. Neben gastrointestinalen Tumoren ist auch ein nicht solider Krebs häufiger.

Adjuvanter PD-L1-Hemmer verhindert Rezidive bei Hochrisiko-Urothelkarzinom

Sind Menschen mit muskelinvasivem Urothelkarzinom für die neoadjuvante platinbasierte Therapie nicht geeignet oder sprechen sie darauf nicht gut an, ist Pembrolizumab eine adjuvante Alternative: Die krankheitsfreie Lebenszeit wird dadurch mehr als verdoppelt.

Duale Checkpointhemmung gegen Melanome verlängert langfristig das Leben

Im Vergleich zu den Überlebenschancen vor der Einführung von Immuncheckpointhemmern (ICI) ist der Fortschritt durch eine ICI-Kombination mit unterschiedlichen Tagets bei fortgeschrittenem Melanom erstaunlich. Das belegen die finalen Ergebnisse der CheckMate-067-Studie und geben Betroffenen "Hoffnung auf Heilung".

Knochenmarktransplantat als Chance für ältere AML-Patienten

Lange Zeit ist die Transplantation von hämatopoetischen Stammzellen nur bei jüngeren Patienten mit akuter myeloischer Leukämie praktiziert worden. Inzwischen profitieren auch Ältere davon. Ergebnisse einer Studie unterstützen dieses Vorgehen.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise