ABSTRACT
INTRODUCTION: In this single-center study of 268 acute myeloid leukemia (AML) patients, we have tested if a subset of 4 routinely employed immunophenotypic stem cell-associated markers correlated with the presence of recurrently mutated genes and if the markers were predictive for mutational status. METHODS: Immunophenotypic data from 268 diagnostic AML samples obtained in 2009-2018 were analyzed retrospectively for the antigens CD34, CD117, CD123, and CLEC12A. Correlation between immunophenotypes and mutations was analyzed by Fischer's exact test. Clinical applicability of the markers for predicting mutational status was evaluated by receiver operating characteristics analyses, where an area under the curve (AUC) of at least 0.85 was accepted as clinically relevant. RESULTS: For a number of genes, the antigen expression differed significantly between mutated and wild-type gene expression. Despite low AUCs, CD123 and CLEC12A correlated with FLT3+NPM1- and FLT3+NPM1+. Three subsets met the AUC requirements (CD34+, CD34+CD117+, and CD34-CD117+) for predicting FLT3-NPM1+ or FLT3+NPM1+. CONCLUSION: The value of immunophenotypes as surrogate markers for mutational status in AML seems limited when employing CD123 and CLEC12A in combination with CD34 and CD117. Defining relevant cutoffs for given markers is challenging and hampered by variation between laboratories and patient groups.
Subject(s)
Antigens, CD34/metabolism , Interleukin-3 Receptor alpha Subunit/metabolism , Lectins, C-Type/metabolism , Leukemia, Myeloid, Acute/diagnosis , Proto-Oncogene Proteins c-kit/metabolism , Receptors, Mitogen/metabolism , Adult , Aged , Aged, 80 and over , Antigens, CD34/genetics , Area Under Curve , Female , Gene Expression Regulation, Neoplastic , Humans , Immunophenotyping , Interleukin-3 Receptor alpha Subunit/genetics , Kaplan-Meier Estimate , Lectins, C-Type/genetics , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Mutation , Nucleophosmin , Proto-Oncogene Proteins c-kit/genetics , ROC Curve , Receptors, Mitogen/genetics , Retrospective Studies , Young AdultABSTRACT
Chronic myeloid neoplasms have susceptibility to transform into acute myeloid leukemia due to attainment of additional molecular lesions. We here describe the kinetics of a del(7q) driven leukemogenesis in a patient with multiple TET2 mutations and JAK2 V617F mutated chronic myeloproliferative neoplasm. The del(7q) emerged in the accelerated phase of disease, which was preceded by a lag phase of almost three years with normalized peripheral blood cell counts. Our results reveal that the del(7q), independently of other lesions, acts as a leukemic driver in this patient and that the stable long-lasting normalization of peripheral blood cell values concealed pending transformation.