Genetic Diversity within Leukemia-Associated Immunophenotype-Defined Subclones in AML

Abstract Acute myeloid leukemia (AML) is a heterogeneous clonal disease and in different patients, combinations of mutations may be found that drive the disease. Also within various leukemic clones with combination co-exist, reflecting evolutionary stages At present, flowcytometry mutational analyses are used to keep track malignant cells during after treatment. Using panels antibodies, abnormal can identified when lineage markers over- or underexpressed, differentiation leads co-expression normally not expressed together on hematopoietic cells. These patient-specific leukemia-associated immunophenptypes (LAIPs) followed treatment, enable early detection resistant recurring Often, several LAIPs present simultaneously patient, but their relationship always clear. In addition, next-generation sequencing mutation-specific PCR follow As clinical consequences MRD-positivity consist high-dose re-induction chemotherapy stem cell transplantation, accurate results highest importance. Although it has already been shown analysis have added value, in-depth information genetic make-up immunophenotypically defined normal subclones AML still scarce. To study similarities differences between by immunophenotyping, we performed an makeup FACS-sorted aberrant 10 cases AML. total, 86 fractions were sorted fully genotyped using error-corrected panel genes recurrently mutated some cases, populations from same patient carried identical mutations, indicating was highly homogeneous, phenotypically all part clone. these monitoring following one would sufficient, or, alternatively, dynamics molecularly accurately show other harbored set mutations. frequently inversely, no clearly clones. molecular carry risk missed. case relevant for resistance relapse, either technique at fail detect MRD positivity. This work underscores currently available, state-of-the-art immunophotyping gene value should simultaneously. We conclude currently, immunophenotypic techniques complementary, parallel order obtain most complete view relapse. time, both further optimized more monoclonal antibodies screened increase resolution. Disclosures No conflicts interest declare.