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Cardiovascular & Hematological Disorders-Drug Targets

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ISSN (Print): 1871-529X
ISSN (Online): 2212-4063

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Research Article

Impact of Leukemia Stem Cells Phenotype Expression on Response to Induction Therapy in Acute Myeloid Leukemia Patients

Author(s): Faez Almohsen* and Subh S. Al-Mudallal

Volume 20, Issue 2, 2020

Page: [145 - 151] Pages: 7

DOI: 10.2174/1871529X19666190719105954

Price: $65

Abstract

Background: Laboratory data suggest that acute myeloid leukemia AML originates from a rare population of cells, termed Leukemic Stem Cells (LSCs) or leukemia-initiating cells, which are capable of self-renewal, proliferation and differentiation into malignant blasts. There is a universal agreement that LSCs lie within the CD34+ compartment of hemopoietic cells and most of leukemic stem cells express the interleukin-3 alpha chain receptor, CD123 and lack CD38. This study aimed to estimate the expression of LSC phenotype in AML patients and to correlate it with response to induction therapy.

Methods: A cohort of 41 patients older than 15 years with newly diagnosed de novo AML were enrolled in this study. They were obtained from the National center of hematology in Baghdad and Baghdad teaching hospital between February and July 2013. The expression of CD34, CD38 and CD123 was assessed by multi-color flow cytometry. LSC positive (LSC+) samples must express CD34 and CD123 and lack the expression of CD38 in >1% of cells. French American British (FAB) classification system was used in this study.

After four weeks of induction therapy; three groups were found: those who reached the Complete morphological Remission (CR), those who failed to reach CR and those who died before the assessment of morphological remission. The last two groups were merged for statistical purposes.

Results: After the course of induction therapy, 41.46% of patients had complete morphological remission while 58.54% of the studied patients failed to reach complete remission. The Complete Remission (CR) rate was higher (53.33%) in patients who were negative for LSC phenotype than patients who were positive for LSC phenotype (34.61%).

Conclusion: LSCs were expressed in 63.41% of AML cases and were in approximate distribution in FAB M3 and non-M3 patients. The expression of LSC phenotype was associated with poor response to induction therapy in AML patients.

Keywords: LSC, leukemia stem cells, AML, CD123, neutropenia, anemia.

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[1]
Lichtman, M.; Kipps, T.; Seligsohn, U. William’s Hematology, 8th ed; McGraw-Hill Companies: New York, 2010, pp. 1277-1279.
[2]
Iraqi Cancer Registry 2009, Baghdad. 2011.
[3]
World life expectancy. [Online]; 2008 [cited 2013 6 30, Available from. http://www.worldlifeexpectancy.com/cause-ofdeath/ leukemia/by-country/
[4]
Hussein, S. Hussein S. Survey of adult de novo acute myeloid cases reported in the medical city in Baghdad through the years (2005-2011);, MSc Thesis, Baghdad University. 2013.
[5]
Vassiliou, G. Vassiliou G. The molecular basis of leukaemia. In Hoffbrand AV. Postgraduate Hematology. 6th ed.:; Willey-Blackwell. , 2011. 380-394
[6]
Buss, E.C.; Ho, A.D. Leukemia stem cells. Int. J. Cancer, 2011, 129(10), 2328-2336.
[http://dx.doi.org/10.1002/ijc.26318] [PMID: 21796620]
[7]
Lapidot, T.; Sirard, C.; Vormoor, J.; Murdoch, B.; Hoang, T.; Caceres-Cortes, J.; Minden, M.; Paterson, B.; Caligiuri, M.A.; Dick, J.E. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature, 1994, 367(6464), 645-648.
[http://dx.doi.org/10.1038/367645a0] [PMID: 7509044]
[8]
Zhao, M.; Zhu, H.; Sajin, R.; Xiao, X.; Deng, Q. Clinical significance of leukemia stem cells immunophenotype expression in patients with acute leukemia. Life Sci. J., 2013, 10(2), 2543-2548.
[9]
Vergez, F.; Green, A.S.; Tamburini, J.; Sarry, J.E.; Gaillard, B.; Cornillet-Lefebvre, P.; Pannetier, M.; Neyret, A.; Chapuis, N.; Ifrah, N.; Dreyfus, F.; Manenti, S.; Demur, C.; Delabesse, E.; Lacombe, C.; Mayeux, P.; Bouscary, D.; Recher, C.; Bardet, V. High levels of CD34+CD38low/-CD123+ blasts are predictive of an adverse outcome in acute myeloid leukemia: A Groupe Ouest-Est des Leucemies Aigues et Maladies du Sang (GOELAMS) study. Haematologica, 2011, 96(12), 1792-1798.
[http://dx.doi.org/10.3324/haematol.2011.047894] [PMID: 21933861]
[10]
Howard, M. Practical Flow Cytometry New Jersey; John Wiley and sons, 2003, pp. 1-5.
[11]
Jordan, C.T. The leukemic stem cell. Best Pract. Res. Clin. Haematol., 2007, 20(1), 13-18.
[http://dx.doi.org/10.1016/j.beha.2006.10.005] [PMID: 17336250]
[12]
Roberts, A.; He, S.; Ritchie, D.; Hertzberg, M.; Kerridge, I.; Durrant, S. A phase I study of anti-CD123 monoclonal antibody (mAb) CSL360 targeting leukemia stem cells (LSC) in AML. J.Clin.l Oncol, 2010. 28(15), abstract nr e13012
[13]
Döhner, H.; Estey, E.H.; Amadori, S.; Appelbaum, F.R.; Büchner, T.; Burnett, A.K.; Dombret, H.; Fenaux, P.; Grimwade, D.; Larson, R.A.; Lo-Coco, F.; Naoe, T.; Niederwieser, D.; Ossenkoppele, G.J.; Sanz, M.A.; Sierra, J.; Tallman, M.S.; Löwenberg, B.; Bloomfield, C.D. LeukemiaNet, E.Diagnosis and management of acute myeloid leukemia in adults: Recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood, 2010, 115(3), 453-574.
[14]
Gerrit, J.S.; Rolf, W.; Angèle, K.; Arjo, P.R.; Alexander, N.S. Specificity of markers of leukemia initiating cells with a new multiparameter flow cytometry based approach; impact for prognostic and therapeutic applications. Blood, 2012. Oral and poster abstracts;53rd ASH annual meeting and exposition
[15]
Testa, U. Atlas of Genetics and Cytogenetics in Oncology and Haematology. [Online].; 2005 [cited 2013, Available from. http://atlasgeneticsoncology.org/Genes/IL3RAID40959chXp22Yp13.html
[16]
Tsunoda, J.; Okada, S.; Suda, J.; Nagayoshi, K.; Nakauchi, H.; Hatake, K.; Miura, Y.; Suda, T. In vivo stem cell function of interleukin-3-induced blast cells. Blood, 1991, 78(2), 318-322.
[PMID: 2070070]
[17]
Buchner, T.; Wolfgang, E. The outcome in AML is predicted by cytogenetics, npm1/flt3 mutation, age and sex, but not by treatment variables. Blood, 2007, 110(593)
[18]
Sarry, J.E.; Murphy, K.; Perry, R.; Sanchez, P.V.; Secreto, A.; Keefer, C.; Swider, C.R.; Strzelecki, A.C.; Cavelier, C.; Récher, C.; Mansat-De Mas, V.; Delabesse, E.; Danet-Desnoyers, G.; Carroll, M. Human acute myelogenous leukemia stem cells are rare and heterogeneous when assayed in NOD/SCID/IL2Rγc-deficient mice. J. Clin. Invest., 2011, 121(1), 384-395.
[http://dx.doi.org/10.1172/JCI41495] [PMID: 21157036]

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