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The singular value of CD34 and CD117 expression for minimal residual disease detection in AML
Leukemia Research 27 (2003) 1069–1070
Letter to the Editor The singular value of CD34 and CD117 expression for minimal residual disease detection in AML Scolnik et al. [1] pointed out that there are low number of studies investigating the value of flow cytometry (FC) to detect minimal residual disease (MRD) in AML and showed their results suggesting the value of quantitative expression of CD34 and CD117 to detect MRD. We would like to extend the findings of previous reports [2–4] showing the value of FC to detect MRD. We studied MRD using aberrant phenotypes (AP) (Table 1) through FC in 12 AML patients, in a single institution, in order to evaluate the potential of this tool to predict relapse. A total of 50,000 events were acquired for all sam-
ples, using the Cell-Quest software program (Becton Dickinson) and the Paint-a-gate software program (Becton Dickinson) to identify residual leukemic cells defined by low SSC versus CD45 intensity and specific AP expression. MRD was evaluated after induction, consolidation and intensification chemotherapy. Our data showed increasing levels of MRD among four patients who relapsed in contrast to patients who remained in continuous complete remission (Fig. 1). Scolnik et al. suggested that quantitative estimation of CD34 and CD117 may be helpful for the detection of MRD in a high proportion of AML patients. Recently, we have shown that the majority of AML cases (28/34) presented CD34 and/or CD117 expression [5]. Moreover, all patients
Fig. 1. MRD levels in AML patients during morphological remission: follow-up of the relapse and remission groups. N: mean values of leukemic cells in 1000 marrow cells; T: time of evaluation (1: post-induction; 2: post-consolidation; 3: post-intensification). 0145-2126/03/$ – see front matter © 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0145-2126(03)00095-X
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Letter to the Editor / Leukemia Research 27 (2003) 1069–1070
Table 1 Aberrant phenotypes used for MRD study in AML patients Case
Aberrant phenotype
1 2 3 4 5 6 7 8 9 10 11 12
CD15+CD117+ CD34+CD11c+; CD56+CD33+ CD15+CD117+; CD13+CD7+; CD13+CD2+ CD15+CD117+; CD34+CD19+ CD11C+CD117+ CD34+CD19+; CD7+CD33+; CD10+CD33+ CD117+CD15+; CD117+CD65+ CD117+CD15+; CD117+11c+; CD117+CD65+ CD117+CD15+; CD117+CD65+ CD117+CD15+; CD34+CD56+ CD117+CD11c+; CD7+CD13+ CD117+CD14+; CD117+CD15+; CD117+CD65+; CD117+CD56+; CD13+CD2+; CD13+CD7+
followed for MRD expressed CD34 and/or CD117 (as shown in Table 1). These data corroborate Scolnik’s findings regarding the importance of CD34 and CD117 for MRD studies, even using different methodologies, either quantitative antigen expression or AP. In summary, we would like to emphasize that FC is a powerful tool for MRD detection in AML. We agree with Scolnik et al. that CD117 and CD34 should be focused as MRD markers and larger series as well as technical standardizing procedures are still needed in order to be widely applicable.
Acknowledgements This study was partially supported by FAPESP (procedure no. 97/02388-1) and CNPq (146469/1999). Contributions. D.M. Bahia Kerbauy contributed to the concept and design, interpreted and analyzed the data, provided drafting of the article, provided critical revision and important intellectual content, collected and assembled the data. E.Y.S. Kimura interpreted and analyzed the data, collected and assembled the data. M.L.L.F. Chauffaille provided study materials/patients. J.O. Bordin obtained a
funding source. J. Kerbauy provided administrative support. M. Yamamoro contributed to the concept and design, interpreted and analyzed the data, provided drafting of the article, provided critical revisions and important intellectual content, and gave final approval. References [1] Scolnik MP, Morilla R, Bracco MME, Catovsky D, Matutes E. CD34 and CD117 are overexpressed in AML and may be valuable to detect minimal residual disease. Leuk Res 2002;26:615–9. [2] San Miguel F, Martinez A, Macedo A, Vidriales MB, López-Berges C, Gonzalez M, et al. Immunophenotyping investigation of minimal residual disease is a useful approach for predicting relapse in acute myeloid leukemia patients. Blood 1997;90(6):2465–70. [3] Venditti A, Buccisiano F, Del Poeta G, Maurillo L, Tamburini A, Cox C, et al. Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia. Blood 2000;96(12): 3945–8. [4] San Miguel F, Vidriales MB, López-Berges C, Diaz-Mediavilla J, Gutierrez N, Cañizo C, et al. Early immunophenotypical evaluation of minimal residual disease in acute myeloid leukemia identifies different patient risk groups and may contribute to pos induction treatment stratification. Blood 2001;98(6):1746–51. [5] Bahia DMM, Yamamoto M, Chauffaille MLLF, Kimura EYS, Bordin JO, Filgueiras MAC, et al. Aberrant phenotypes in acute myeloid leukemia: a high frequency and clinical significance. Haematologica 2001;86:801–6.
D.M. Bahia Kerbauy, E.Y.S. Kimura M.L.L.F. Chauffaille, J.O. Bordin J. Kerbauy, M. Yamamoto∗ Disciplina de Hematologia e Hemoterapia Escola Paulista de Medicina Universidade Federal de São Paulo, R. Botucatu 740 V. Clementino, Sao Paulo CEP 04023-900 Brazil ∗ Corresponding author. Fax: +55-11-55718806 E-mail address: [email protected] (M. Yamamoto) 3 March 2003
Letter to the Editor The singular value of CD34 and CD117 expression for minimal residual disease detection in AML Scolnik et al. [1] pointed out that there are low number of studies investigating the value of flow cytometry (FC) to detect minimal residual disease (MRD) in AML and showed their results suggesting the value of quantitative expression of CD34 and CD117 to detect MRD. We would like to extend the findings of previous reports [2–4] showing the value of FC to detect MRD. We studied MRD using aberrant phenotypes (AP) (Table 1) through FC in 12 AML patients, in a single institution, in order to evaluate the potential of this tool to predict relapse. A total of 50,000 events were acquired for all sam-
ples, using the Cell-Quest software program (Becton Dickinson) and the Paint-a-gate software program (Becton Dickinson) to identify residual leukemic cells defined by low SSC versus CD45 intensity and specific AP expression. MRD was evaluated after induction, consolidation and intensification chemotherapy. Our data showed increasing levels of MRD among four patients who relapsed in contrast to patients who remained in continuous complete remission (Fig. 1). Scolnik et al. suggested that quantitative estimation of CD34 and CD117 may be helpful for the detection of MRD in a high proportion of AML patients. Recently, we have shown that the majority of AML cases (28/34) presented CD34 and/or CD117 expression [5]. Moreover, all patients
Fig. 1. MRD levels in AML patients during morphological remission: follow-up of the relapse and remission groups. N: mean values of leukemic cells in 1000 marrow cells; T: time of evaluation (1: post-induction; 2: post-consolidation; 3: post-intensification). 0145-2126/03/$ – see front matter © 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0145-2126(03)00095-X
1070
Letter to the Editor / Leukemia Research 27 (2003) 1069–1070
Table 1 Aberrant phenotypes used for MRD study in AML patients Case
Aberrant phenotype
1 2 3 4 5 6 7 8 9 10 11 12
CD15+CD117+ CD34+CD11c+; CD56+CD33+ CD15+CD117+; CD13+CD7+; CD13+CD2+ CD15+CD117+; CD34+CD19+ CD11C+CD117+ CD34+CD19+; CD7+CD33+; CD10+CD33+ CD117+CD15+; CD117+CD65+ CD117+CD15+; CD117+11c+; CD117+CD65+ CD117+CD15+; CD117+CD65+ CD117+CD15+; CD34+CD56+ CD117+CD11c+; CD7+CD13+ CD117+CD14+; CD117+CD15+; CD117+CD65+; CD117+CD56+; CD13+CD2+; CD13+CD7+
followed for MRD expressed CD34 and/or CD117 (as shown in Table 1). These data corroborate Scolnik’s findings regarding the importance of CD34 and CD117 for MRD studies, even using different methodologies, either quantitative antigen expression or AP. In summary, we would like to emphasize that FC is a powerful tool for MRD detection in AML. We agree with Scolnik et al. that CD117 and CD34 should be focused as MRD markers and larger series as well as technical standardizing procedures are still needed in order to be widely applicable.
Acknowledgements This study was partially supported by FAPESP (procedure no. 97/02388-1) and CNPq (146469/1999). Contributions. D.M. Bahia Kerbauy contributed to the concept and design, interpreted and analyzed the data, provided drafting of the article, provided critical revision and important intellectual content, collected and assembled the data. E.Y.S. Kimura interpreted and analyzed the data, collected and assembled the data. M.L.L.F. Chauffaille provided study materials/patients. J.O. Bordin obtained a
funding source. J. Kerbauy provided administrative support. M. Yamamoro contributed to the concept and design, interpreted and analyzed the data, provided drafting of the article, provided critical revisions and important intellectual content, and gave final approval. References [1] Scolnik MP, Morilla R, Bracco MME, Catovsky D, Matutes E. CD34 and CD117 are overexpressed in AML and may be valuable to detect minimal residual disease. Leuk Res 2002;26:615–9. [2] San Miguel F, Martinez A, Macedo A, Vidriales MB, López-Berges C, Gonzalez M, et al. Immunophenotyping investigation of minimal residual disease is a useful approach for predicting relapse in acute myeloid leukemia patients. Blood 1997;90(6):2465–70. [3] Venditti A, Buccisiano F, Del Poeta G, Maurillo L, Tamburini A, Cox C, et al. Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia. Blood 2000;96(12): 3945–8. [4] San Miguel F, Vidriales MB, López-Berges C, Diaz-Mediavilla J, Gutierrez N, Cañizo C, et al. Early immunophenotypical evaluation of minimal residual disease in acute myeloid leukemia identifies different patient risk groups and may contribute to pos induction treatment stratification. Blood 2001;98(6):1746–51. [5] Bahia DMM, Yamamoto M, Chauffaille MLLF, Kimura EYS, Bordin JO, Filgueiras MAC, et al. Aberrant phenotypes in acute myeloid leukemia: a high frequency and clinical significance. Haematologica 2001;86:801–6.
D.M. Bahia Kerbauy, E.Y.S. Kimura M.L.L.F. Chauffaille, J.O. Bordin J. Kerbauy, M. Yamamoto∗ Disciplina de Hematologia e Hemoterapia Escola Paulista de Medicina Universidade Federal de São Paulo, R. Botucatu 740 V. Clementino, Sao Paulo CEP 04023-900 Brazil ∗ Corresponding author. Fax: +55-11-55718806 E-mail address: [email protected] (M. Yamamoto) 3 March 2003