Cluster of differentiation 96 as a leukemia stem cell-specific marker and a factor for prognosis evaluation in leukemia

Du,Wen; Hu,Yanjie; Lu,Cong; Li,Juan; Liu,Wei; He,Yanli; Wang,Ping; Cheng,Chen; Hu,Yu; Huang,Shiang; Yao,Junxia; Zheng,Jin'e

doi:10.3892/mco.2015.552

Cluster of differentiation 96 as a leukemia stem cell-specific marker and a factor for prognosis evaluation in leukemia

Authors:
- Wen Du
- Yanjie Hu
- Cong Lu
- Juan Li
- Wei Liu
- Yanli He
- Ping Wang
- Chen Cheng
- Yu Hu
- Shiang Huang
- Junxia Yao
- Jin'e Zheng
View Affiliations

Affiliations: Center for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Tumor Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: April 24, 2015 https://doi.org/10.3892/mco.2015.552
Pages: 833-838

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Resistance to chemotherapy is a major challenge for leukemia treatment. It has been suggested that leukemia stem cells (LSCs), a small pool of self‑renewing leukemic cells, play important roles in development of chemotherapy resistance. The expression of cluster of differentiation 96 (CD96), a potential marker for LSCs, was investigated in CD34+CD38‑ cells of 105 acute leukemia (AL) patients by flow cytometry. The data showed that all the CD34+, CD34+CD38‑ and CD34+CD38‑CD96+ proportions were much higher in AL compared to the normal control (P<0.01), while a clear difference was identified in the CD34+CD38‑ and CD34+CD38‑CD96+ proportions between acute lymphoid leukemia and acute myeloid leukemia (AML). However, all the AML patients with >15% CD34+CD38‑ cells achieved complete remission (CR), suggesting that as an LSC‑rich population, the amount of CD34+CD38‑ cells may not be positively associated with the proportion of refractory LSCs. The mean percentage of the co‑presence of CD96 expression itself was similar in AML patients with CR and non‑CR (P>0.05). However, the CR rate was significantly higher in the AML population with <10% CD96 expressed, which indicated that a distinct sub‑group of CD34+CD38‑CD96+ cells may still contribute to the drug resistance or poor prognosis.

View Figures

View References

1	Reya T, Morrison SJ, Clarke MF and Weissman IL: Stem cells, cancer and cancer stem cells. Nature. 414:105–111. 2001. View Article : Google Scholar : PubMed/NCBI
2	Passegué E, Jamieson CH, Ailles LE and Weissman IL: Normal and leukemic hematopoiesis: Are leukemias a stem cell disorder or a reacquisition of stem cell characteristics? Proc Natl Acad Sci USA. 100:(Suppl 1). 11842–11849. 2003. View Article : Google Scholar : PubMed/NCBI
3	Warner JK, Wang JCY, Hope KJ, Jin L and Dick JE: Concepts of human leukemic development. Oncogene. 23:7164–7177. 2004. View Article : Google Scholar : PubMed/NCBI
4	Huntly BJ and Gilliland DG: Leukaemia stem cells and the evolution of cancer-stem-cell research. Nat Rev Cancer. 5:311–321. 2005. View Article : Google Scholar : PubMed/NCBI
5	Weissman I: Stem cell research: Paths to cancer therapies and regenerative medicine. JAMA. 294:1359–1366. 2005. View Article : Google Scholar : PubMed/NCBI
6	Costello R, Mallet F, Chambost H, Sainty D, Arnoulet C, Gastaut JA and Olive D: The immunophenotype of minimally differentiated acute myeloid leukemia (AML-M0): Reduced immunogenicity and high frequency of CD34⁺/CD38⁻ leukemic progenitors. Leukemia. 13:1513–1518. 1999. View Article : Google Scholar : PubMed/NCBI
7	van Rhenen A, Feller N, Kelder A, Westra AH, Rombouts E, Zweegman S, van der Pol MA, Waisfisz Q, Ossenkoppele GJ and Schuurhuis GJ: High stem cell frequency in acute myeloid leukemia at diagnosis predicts high minimal residual disease and poor survival. Clin Cancer Res. 11:6520–6527. 2005. View Article : Google Scholar : PubMed/NCBI
8	Bonnet D and Dick JE: Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 3:730–737. 1997. View Article : Google Scholar : PubMed/NCBI
9	Malaise M, Steinbach D and Corbacioglu S: Clinical implications of c-Kit mutations in acute myelogenous leukemia. Curr Hematol Malig Rep. 4:77–82. 2009. View Article : Google Scholar : PubMed/NCBI
10	Wakita S, Yamaguchi H, Miyake K, Mitamura Y, Kosaka F, Dan K and Inokuchi K: Importance of c-kit mutation detection method sensitivity in prognostic analyses of t(8;21)(q22;q22) acute myeloid leukemia. Leukemia. 25:1423–1432. 2011. View Article : Google Scholar : PubMed/NCBI
11	Park SH, Chi HS, Min SK, Park BG, Jang S and Park CJ: Prognostic impact of c-KIT mutations in core binding factor acute myeloid leukemia. Leuk Res. 35:1376–1383. 2011. View Article : Google Scholar : PubMed/NCBI
12	Chao MP, Alizadeh AA, Tang C, Jan M, Weissman-Tsukamoto R, Zhao F, Park CY, Weissman IL and Majeti R: Therapeutic antibody targeting of CD47 eliminates human acute lymphoblastic leukemia. Cancer Res. 71:1374–1384. 2011. View Article : Google Scholar : PubMed/NCBI
13	Gerber JM, Smith BD, Ngwang B, Zhang H, Vala MS, Morsberger L, Galkin S, Collector MI, Perkins B, Levis MJ, et al: A clinically relevant population of leukemic CD34(+)CD38(–) cells in acute myeloid leukemia. Blood. 119:3571–3577. 2012. View Article : Google Scholar : PubMed/NCBI
14	Meyer D, Seth S, Albrecht J, Maier MK, du Pasquier L, Ravens I, Dreyer L, Burger R, Gramatzki M, Schwinzer R, et al: CD96 interaction with CD155 via tts first Ig-like domain is modulated by alternative splicing or mutations in distal Ig-like domains. J Biol Chem. 284:2235–2244. 2009. View Article : Google Scholar : PubMed/NCBI
15	Fuchs A, Cella M, Giurisato E, Shaw AS and Colonna M: Cutting edge: CD96 (tactile) promotes NK cell-target cell adhesion by interacting with the poliovirus receptor (CD155). J Immunol. 172:3994–3998. 2004. View Article : Google Scholar : PubMed/NCBI
16	Hosen N, Park CY, Tatsumi N, Oji Y, Sugiyama H, Gramatzki M, Krensky AM and Weissman IL: CD96 is a leukemic stem cell-specific marker in human acute myeloid leukemia. Proc Natl Acad Sci USA. 104:11008–11013. 2007. View Article : Google Scholar : PubMed/NCBI
17	Gramatzki M, Ludwig WD, Burger R, Moos P, Rohwer P, Grünert C, Sendler A, Kalden JR, Andreesen R, Henschke F, et al: Antibodies TC-12 (‘unique’) and TH-111 (CD96) characterize T-cell acute lymphoblastic leukemia and a subgroup of acute myeloid leukemia. Exp Hematol. 26:1209–1214. 1998.PubMed/NCBI
18	Löwenberg B, Downing JR and Burnett A: Acute myeloid leukemia. N Engl J Med. 341:1051–1062. 1999. View Article : Google Scholar : PubMed/NCBI
19	Wang PL, O'Farrell S, Clayberger C and Krensky AM: Identification and molecular cloning of tactile. A novel human T cell activation antigen that is a member of the Ig gene superfamily. J Immunol. 148:2600–2608. 1992.PubMed/NCBI
20	Ebinger M, Witte KE, Ahlers J, Schӓfer I, André M, Kerst G, Scheel-Walter HG, Lang P and Handgretinger R: High frequency of immature cells at diagnosis predicts high minimal residual disease level in childhood acute lymphoblastic leukemia. Leuk Res. 34:1139–1142. 2010. View Article : Google Scholar : PubMed/NCBI
21	Witte KE, Ahlers J, Schӓfer I, André M, Kerst G, Scheel-Walter HG, Schwarze CP, Pfeiffer M, Lang P, Handgretinger R, et al: High proportion of leukemic stem cells at diagnosis is correlated with unfavorable prognosis in childhood acute myeloid leukemia. Pediatr Hematol Oncol. 28:91–99. 2011. View Article : Google Scholar : PubMed/NCBI
22	Castor A, Nilsson L, Astrand-Grundström I, Buitenhuis M, Ramirez C, Anderson K, Strömbeck B, Garwicz S, Békássy AN, Schmiegelow K, et al: Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia. Nat Med. 11:630–637. 2005. View Article : Google Scholar : PubMed/NCBI
23	Hong D, Gupta R, Ancliff P, Atzberger A, Brown J, Soneji S, Green J, Colman S, Piacibello W, Buckle V, et al: Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia. Science. 319:336–339. 2008. View Article : Google Scholar : PubMed/NCBI
24	Adams GP and Weiner LM: Monoclonal antibody therapy of cancer. Nat Biotechnol. 23:1147–1157. 2005. View Article : Google Scholar : PubMed/NCBI