Significance of CD49f in diagnosis of minimal residual disease in pediatric acute leukemia

Tuba Kurt; Ebru Yılmaz; Ekrem Ünal; Musa Karakükcü; Türkan Patiroğlu

Research Article

Significance of CD49f in diagnosis of minimal residual disease in pediatric acute leukemia

Year 2023, Volume: 40 Issue: 3, 426 - 430, 30.09.2023

Tuba Kurt Ebru Yılmaz Ekrem Ünal Musa Karakükcü Türkan Patiroğlu

Abstract

Minimal residual disease (MRD) is the most important prognostic indicator in acute lymphoblastic leukemia (ALL) in childhood. Multiparametric flow cytometry (FCM) is a technique that is often used to determine MRD, and many markers have been identified. Another marker examined in the MRD analysis is CD49f. We aimed to determine the importance of CD49f expression in MRD detection. Immunophenotyping MRD and CD49f expressions were performed in patients with Pre-B cell ALL at the diagnosis, and on the day 15. 27 patients were included (F/M: 10/17). The mean age was 6.6±4.8 years. 6 (22.2%) patients were in the standard risk group, 14 (51.9%) patients were in the intermediate risk group, and 7 (25.9%) patients were in the high-risk group. MRD was detected in 15 (55.6%) patients. Cytomorphological remission was observed in 21 (77.7%) patients on the 15th day. 10 of these patients (66.6%) were MRD positive. CD49f levels at diagnosis and at 15th day were mean 38.4 ± 22.1 and 5.4±12.6, respectively. A significant decrease in CD49f expression was observed at follow up (p=0.00). Mean CD49f levels in MRD positive and MRD negative patients were 7.8±17 and 2.8±2 at day 15, respectively (p=0.64). There was no correlation between MRD and CD49f at day 15 (p=0.54). We observed that leukemic blasts express CD49f at a high rate, and this expression continues to decrease on the 15th day. We concluded that studies including more patients are required to assess the performance and importance of CD49f as an indicator in MRD.

Keywords

Acute lymphoblastic leukemia, minimal residual disease, CD49f, Acute lymphoblastic leukemia, minimal residual disease, CD49f

Supporting Institution

Erciyes University Scientific Research Projects Coordination Unit

Project Number

(TSU-12-3805).

References

1. Pui C-H, Evans WE. Acute lymphoblastic leukemia. N Engl J Med 2006; 354:166-167.
2. Vrooman LM, Silverman LB. Treatment of Childhood Acute Lymphoblastic Leukemia: Prognostic Factors and Clinical Advances. Curr Hematol Malig Rep. 2016;11(5):385-94.
3. Vrooman LM, Silverman LB. Treatment of Childhood Acute Lymphoblastic Leukemia: Prognostic Factors and Clinical Advances. Curr Hematol Malig Rep. 2016 Oct;11(5):385-94.
4. Berry DA, Zhou S, Higley H, Mukundan L, Fu S, Reaman GH, et al. Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: a meta-analysis. JAMA Oncol. 2017;3(7): e170580.
5. Shaver AC, Seegmiller AC. B Lymphoblastic leukemia minimal residual disease assessment by flow cytometric analysis. Clin Lab Med. 2017;37(4):771-785.
6. Kruse A, Abdel-Azim N, Kim HN, Ruan Y, Phan V, et al. Minimal Residual Disease Detection in Acute Lymphoblastic Leukemia. Int J Mol Sci. 2020; 21(3):1054.
7. Correia RP, Bento LC, de Sousa FA, Barroso RS, Campregher PV, Bacal NS. How I investigate minimal residual disease in acute lymphoblastic leukemia. Int J Lab Hematol. 2021; 43(3):354-363.
8. Coustan-Smith E, Song G, Clark C, Key L, Liu P, Mehrpooya M, et al. New markers for minimal residual disease detection in acute lymphoblastic leukemia. Blood. 2011; 117(23):6267-76.
9. DiGiuseppe JA, Fuller SG, Borowitz MJ. Overexpression of CD49f in precursor B-cell acute lymphoblastic leukemia: Potential usefulness in minimal residual disease detection. Cytometry Part B. 2009; 76B:150–155.
10. Hazar V, Karasu GT, Uygun V ve ark. Childhood acute lymphoblastic leukemia in Turkey: factors influencing treatment and outcome: a single center experience. J Pediatr Hematol Oncol 2010; 32:317-22.
11. Heikamp EB, Pui CH. Next-Generation Evaluation and Treatment of Pediatric Acute Lymphoblastic Leukemia. J Pediatr. 2018; 203:14-24.
12. Kusenda J, Fajtova M, Kovarikova A. Monitoring of minimal residual disease in acute leukemia by multiparametric flow cytometry. Neoplasma. 2014;61(2):119-27.
13. Salari F, Shahjahani M, Shahrabi S, Saki N. Minimal residual disease in acute lymphoblastic leukemia: optimal methods and clinical relevance, pitfalls, and recent approaches. Med Oncol. 2014;31(11):266.
14. Xue YJ, Wang Y, Jia YP, Zuo YX, Wu J, Lu AD, et al. The role of minimal residual disease in specific subtypes of pediatric acute lymphoblastic leukemia. Int J Hematol. 2021;113(4):547-555.
15. Macedo A, Orfao A, Ciudad J, Gonzalez M, Vidriales B, Lopez-Berges MC, et al. Phenotypic analysis of CD 34 subpopulations in normal human bone marrow and its application for the detection of minimal residual disease. Leukemia. 1995; 9:1896-901.
16. Ladetto M, Böttcher S, Kröger, Pulsipher MA, Bader P. Methods and role of minimal residual disease after stem cell transplantation. Bone Marrow Transplant. 2019; 54:681–690.
17. Denys B, van der Sluijs-Gelling A.J, Homburg C, van der Schoot CE, de Haas V, Philippe J, et al. Improved flow cytometric detection of minimal residual disease in childhood acute lymphoblastic leukemia. Leukemia. 2013; 27:635–641.
18. DiGiuseppe JA, Tadmor MD, Pe’er D. Detection of Minimal Residual Disease in B Lymphoblastic Leukemia Using viSNE. Cytometry Part B. 2015; 88B:294–304.
19. Collins K, Cardinali JL, Mnayer LO, DiGiuseppe JA. CD49f protein expression varies among genetic subgroups of B lymphoblastic leukemia and is distinctly low in KMT2A-rearranged cases. Cytometry B Clin Cytom. 2021;100(2):243-248.
20. Yao H, Price TT, Cantelli G, Ngo B, Warner MJ, Olivere L, et al. Leukaemia hijacks a neural mechanism to invade the central nervous system. Nature. 2018;560(7716):55-60.

Year 2023, Volume: 40 Issue: 3, 426 - 430, 30.09.2023

Tuba Kurt Ebru Yılmaz Ekrem Ünal Musa Karakükcü Türkan Patiroğlu

Abstract

Keywords

Acute lymphoblastic leukemia, minimal residual disease, CD49f

Project Number

(TSU-12-3805).

References

1. Pui C-H, Evans WE. Acute lymphoblastic leukemia. N Engl J Med 2006; 354:166-167.
2. Vrooman LM, Silverman LB. Treatment of Childhood Acute Lymphoblastic Leukemia: Prognostic Factors and Clinical Advances. Curr Hematol Malig Rep. 2016;11(5):385-94.
3. Vrooman LM, Silverman LB. Treatment of Childhood Acute Lymphoblastic Leukemia: Prognostic Factors and Clinical Advances. Curr Hematol Malig Rep. 2016 Oct;11(5):385-94.
4. Berry DA, Zhou S, Higley H, Mukundan L, Fu S, Reaman GH, et al. Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: a meta-analysis. JAMA Oncol. 2017;3(7): e170580.
5. Shaver AC, Seegmiller AC. B Lymphoblastic leukemia minimal residual disease assessment by flow cytometric analysis. Clin Lab Med. 2017;37(4):771-785.
6. Kruse A, Abdel-Azim N, Kim HN, Ruan Y, Phan V, et al. Minimal Residual Disease Detection in Acute Lymphoblastic Leukemia. Int J Mol Sci. 2020; 21(3):1054.
7. Correia RP, Bento LC, de Sousa FA, Barroso RS, Campregher PV, Bacal NS. How I investigate minimal residual disease in acute lymphoblastic leukemia. Int J Lab Hematol. 2021; 43(3):354-363.
8. Coustan-Smith E, Song G, Clark C, Key L, Liu P, Mehrpooya M, et al. New markers for minimal residual disease detection in acute lymphoblastic leukemia. Blood. 2011; 117(23):6267-76.
9. DiGiuseppe JA, Fuller SG, Borowitz MJ. Overexpression of CD49f in precursor B-cell acute lymphoblastic leukemia: Potential usefulness in minimal residual disease detection. Cytometry Part B. 2009; 76B:150–155.
10. Hazar V, Karasu GT, Uygun V ve ark. Childhood acute lymphoblastic leukemia in Turkey: factors influencing treatment and outcome: a single center experience. J Pediatr Hematol Oncol 2010; 32:317-22.
11. Heikamp EB, Pui CH. Next-Generation Evaluation and Treatment of Pediatric Acute Lymphoblastic Leukemia. J Pediatr. 2018; 203:14-24.
12. Kusenda J, Fajtova M, Kovarikova A. Monitoring of minimal residual disease in acute leukemia by multiparametric flow cytometry. Neoplasma. 2014;61(2):119-27.
13. Salari F, Shahjahani M, Shahrabi S, Saki N. Minimal residual disease in acute lymphoblastic leukemia: optimal methods and clinical relevance, pitfalls, and recent approaches. Med Oncol. 2014;31(11):266.
14. Xue YJ, Wang Y, Jia YP, Zuo YX, Wu J, Lu AD, et al. The role of minimal residual disease in specific subtypes of pediatric acute lymphoblastic leukemia. Int J Hematol. 2021;113(4):547-555.
15. Macedo A, Orfao A, Ciudad J, Gonzalez M, Vidriales B, Lopez-Berges MC, et al. Phenotypic analysis of CD 34 subpopulations in normal human bone marrow and its application for the detection of minimal residual disease. Leukemia. 1995; 9:1896-901.
16. Ladetto M, Böttcher S, Kröger, Pulsipher MA, Bader P. Methods and role of minimal residual disease after stem cell transplantation. Bone Marrow Transplant. 2019; 54:681–690.
17. Denys B, van der Sluijs-Gelling A.J, Homburg C, van der Schoot CE, de Haas V, Philippe J, et al. Improved flow cytometric detection of minimal residual disease in childhood acute lymphoblastic leukemia. Leukemia. 2013; 27:635–641.
18. DiGiuseppe JA, Tadmor MD, Pe’er D. Detection of Minimal Residual Disease in B Lymphoblastic Leukemia Using viSNE. Cytometry Part B. 2015; 88B:294–304.
19. Collins K, Cardinali JL, Mnayer LO, DiGiuseppe JA. CD49f protein expression varies among genetic subgroups of B lymphoblastic leukemia and is distinctly low in KMT2A-rearranged cases. Cytometry B Clin Cytom. 2021;100(2):243-248.
20. Yao H, Price TT, Cantelli G, Ngo B, Warner MJ, Olivere L, et al. Leukaemia hijacks a neural mechanism to invade the central nervous system. Nature. 2018;560(7716):55-60.

There are 20 citations in total.

Details

Primary Language	English
Subjects	Health Care Administration
Journal Section	Research Article
Authors	Tuba Kurt 0000-0003-3711-8347 Ebru Yılmaz 0000-0003-4802-0986 Ekrem Ünal 0000-0002-2691-4826 Musa Karakükcü 0000-0003-2015-3541 Türkan Patiroğlu 0000-0003-2471-764X
Project Number	(TSU-12-3805).
Early Pub Date	October 6, 2023
Publication Date	September 30, 2023
Submission Date	December 5, 2022
Acceptance Date	June 20, 2023
Published in Issue	Year 2023 Volume: 40 Issue: 3

Cite

APA	Kurt, T., Yılmaz, E., Ünal, E., Karakükcü, M., et al. (2023). Significance of CD49f in diagnosis of minimal residual disease in pediatric acute leukemia. Journal of Experimental and Clinical Medicine, 40(3), 426-430.
AMA	Kurt T, Yılmaz E, Ünal E, Karakükcü M, Patiroğlu T. Significance of CD49f in diagnosis of minimal residual disease in pediatric acute leukemia. J. Exp. Clin. Med. September 2023;40(3):426-430.
Chicago	Kurt, Tuba, Ebru Yılmaz, Ekrem Ünal, Musa Karakükcü, and Türkan Patiroğlu. “Significance of CD49f in Diagnosis of Minimal Residual Disease in Pediatric Acute Leukemia”. Journal of Experimental and Clinical Medicine 40, no. 3 (September 2023): 426-30.
EndNote	Kurt T, Yılmaz E, Ünal E, Karakükcü M, Patiroğlu T (September 1, 2023) Significance of CD49f in diagnosis of minimal residual disease in pediatric acute leukemia. Journal of Experimental and Clinical Medicine 40 3 426–430.
IEEE	T. Kurt, E. Yılmaz, E. Ünal, M. Karakükcü, and T. Patiroğlu, “Significance of CD49f in diagnosis of minimal residual disease in pediatric acute leukemia”, J. Exp. Clin. Med., vol. 40, no. 3, pp. 426–430, 2023.
ISNAD	Kurt, Tuba et al. “Significance of CD49f in Diagnosis of Minimal Residual Disease in Pediatric Acute Leukemia”. Journal of Experimental and Clinical Medicine 40/3 (September 2023), 426-430.
JAMA	Kurt T, Yılmaz E, Ünal E, Karakükcü M, Patiroğlu T. Significance of CD49f in diagnosis of minimal residual disease in pediatric acute leukemia. J. Exp. Clin. Med. 2023;40:426–430.
MLA	Kurt, Tuba et al. “Significance of CD49f in Diagnosis of Minimal Residual Disease in Pediatric Acute Leukemia”. Journal of Experimental and Clinical Medicine, vol. 40, no. 3, 2023, pp. 426-30.
Vancouver	Kurt T, Yılmaz E, Ünal E, Karakükcü M, Patiroğlu T. Significance of CD49f in diagnosis of minimal residual disease in pediatric acute leukemia. J. Exp. Clin. Med. 2023;40(3):426-30.

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