High prognostic value of minimal residual disease detected by flow-cytometry-enhanced fluorescence in situ hybridization in core-binding factor acute myeloid leukemia (CBF-AML).
Acute myeloid leukemia (AML) is generally regarded as a disorder of stem cells, known as leukemic initiating cells (LICs), which initiate the disease and contribute to relapses. Although the phenotype of these cells remains unclear in most patients, they are enriched within the CD34(+)CD38(-) population. In core-binding factor (CBF) AML, the cytogenetic abnormalities also exist in LIC. The aim of this study was to determine the prognostic power of minimal residual disease (MRD) measured by fluorescence in situ hybridization (FISH) in CD34(+)CD38(-) cells sorted by flow cytometry at different periods during therapy. Thirty-six patients under 65 years of age with de novo CBF-AML treated with intensive chemotherapy were retrospectively included in this study. Correlations with relapse-free survival (RFS) and overall survival were evaluated with univariate and multivariate analyses. FISH efficiently identified LICs in the CD34(+)CD38(-) population. The presence of FISH(+)CD34(+)CD38(-) cells before consolidation was negatively associated with cumulative incidence of relapse (64 vs 18 %, P = .012), which showed prognostic value for RFS (12 vs 68 %, P = .008) and OS (11 vs 75 %, P = .0005), and retained prognostic significance for RFS in multivariate analysis. The detection of FISH(+)CD34(+)CD38(-) cells before consolidation therapy significantly correlated with long-term survival. Fluorescence-activated cell sorting (FACS)-FISH could be potentially adopted as a MRD monitor approach in clinical practice to identify CBF-AML patients at risk of treatment failure during therapy.
Department of Hematology, Institute of Hematology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, 200433, Shanghai, China.
Libing
L
Wang
Lei
L
Gao
Sheng
S
Xu
Shenglan
S
Gong
Min
M
Liu
Huiying
H
Qiu
Xiaoqian
X
Xu
Xiong
X
Ni
Li
L
Chen
Shuqing
S
Lu
Jie
J
Chen
Xianmin
X
Song
Weiping
W
Zhang
Jianmin
J
Yang
Xiaoxia
X
Hu
Jianmin
J
Wang
D051997:ADP-ribosyl Cyclase 1; D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002469:Cell Separation / Q000379:methods; D002869:Chromosome Aberrations; D060830:Consolidation Chemotherapy; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D005434:Flow Cytometry / Q000379:methods*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D014411:Neoplastic Stem Cells / Q000737:chemistry* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D000075142:RUNX1 Translocation Partner 1 Protein; D055815:Young Adult
C107844:AML1-ETO fusion protein, human; D018952:Antigens, CD34; C095514:CBFbeta-MYH11 fusion protein; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D003561:Cytarabine; D051997:ADP-ribosyl Cyclase 1; D003630:Daunorubicin