The presence of leukaemia‐associated phenotypes is an independent predictor of induction failure in acute myeloid leukaemia

Abstract

Immunophenotyping of acute myeloid leukaemia (AML) has controversial implications with regards to prognosis. The aims of the present study were to determine the frequency of leukaemia-associated phenotypes (LAP) in AML and to correlate their presence with response to induction chemotherapy. We analysed bone marrow samples at diagnosis from 84 AML patients using triple staining flow cytometry with routine standard panel of monoclonal antibodies. The association of LAP and response to induction chemotherapy was evaluated retrospectively. LAP were observed in 54 (64%) patients: lineage infidelity in 19 (35%), asynchronous antigen expression in 28 (52%), and lack of expected lineage specific antigens in 19 (35%). Significant correlation was found between LAP and responses to induction chemotherapy. Response to induction chemotherapy was more frequent in the absence of LAP (P < 0.05, estimated risk ratio of 1.6, 95%CI, 1.0-2.6) in a multivariate analysis. In conclusion, our data show the presence of LAP in AML is an independent predictor for response to induction chemotherapy and risk of relapse and should be considered for counselling patients and planning therapy.

Leukemia‐associated aberrant immunophenotype in patients with acute myeloid leukemia: changes at refractory disease or first relapse and clinicopathological findings

“…Underexpression of CD34, CD117, and HLA‐DR was found in small fraction of the cases. These findings are consistent with the previous reports . Other aberrantly expressed lymphoid markers including CD2 and CD5 were identified, but in much lower frequency.…”

The Role of Multiparameter Flow Cytometry for Detection of Minimal Residual Disease in Acute Myeloid Leukemia

“…31 In contrast, recent data indicate that immunologic monitoring may be applicable to more than 90% of patients with AML when pursuing a comprehensive approach. 10,11,14,29 Additionally, sensitivity of MRD detection can range as high as 1 leukemic cell per 10 4 to 10 5 normal cells. Furthermore, rapid and accurate quantification can be achieved.…”

“…[24][25][26][27] In the experience of some groups, serial dilution experiments of leukemic cells with normal BM cells determined that the detection limit of MFC ranges between 10 -4 and 10 -5 . 3,11,14,19,28 Advantages and Drawbacks of MFC for Detecting MRD Polymerase chain reaction (PCR)-based quantification of MRD has high sensitivity, and the proportion of AML cases amenable to PCR detection may be significantly increased by targeting length mutations of the Fms-like tyrosine kinase 3 (FLT3) gene and partial tandem duplications within the MLL gene, in addition to the fusion transcripts AML1-ETO, CBFb-MYH11, and PML-RARa. 29 Although PCR techniques seem to be promising for monitoring MRD in AML, they are currently applicable only on leukemias that bear specific DNA markers such as fused genes.…”

“…[7][8][9][10][11] These LAPs are not present or only very infrequently present on normal blood or BM cells. For AML, the most relevant types of aberrations include the following: (1) asynchronous antigen expression (simultaneous expression of early and late markers in 1 cell, such as coexpression of the CD34 and CD15 antigens); (2) lineage infidelity (expression of the lymphoid-associated markers, ie, CD2, CD3, CD5, CD7, CD10, and CD19 on myeloid blast cells); (3) antigen overexpression (abnormally increased expression of a certain antigen per cell); (4) aberrant light-scatter properties (the expression of lymphoidassociated antigens in blast cells displaying a relatively high forward scatter and side scatter, corresponding to normal myeloid cells) 7,[11][12][13][14] ; and (5) absence of lineage-specific antigens (absence of antigen expression such as CD13 and CD33 on myeloid blasts). Current immunologic strategies for detecting MRD rely on combinations of leukocyte markers normally not seen in peripheral blood and BM.…”

The use of receiver operating characteristic analysis for detection of minimal residual disease using five‐color multiparameter flow cytometry in acute myeloid leukemia identifies patients with high risk of relapse

“…CD45/CD34/CD117 were used in combination with different myeloid and lymphoid markers in a five-color combination to increase the sensitivity of the LAP detection. This was done to obtain a maximum advantage, incorporating various permutations and combinations, of the five-color MFC in defining the LAPs as we previously described (7,23). The screening panel was CD7FITC/CD13PE/CD45PC5, CD19FITC/CD10PE/ CD45PC5, CD34FITC/CD33PE/CD45PC5, CD14FITC/ CD56PE/CD45PC5, HLA-DRFITC/CD45PC5, CD15FITC/ CD117PE/CD45PC5, MPO FITC/CD45PC5, TdT FITC/ CD45PC5, and CD45PC5/SNEG.…”