Dynamic transcriptomic tracking directs the treatment for acute leukemia of ambiguous lineage

Acute leukemia of ambiguous lineage (ALAL) is a rare subtype of acute leukemia characterized by the lack of straightforward myeloid or lymphoid lineage commitment. Currently, no treatment guidelines are commonly-accepted for ALAL. Herein, we have established an molecular-guided therapeutic approach to classify ALAL as either possessing an transciptional profile with a tendency towards acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). A three and a half years perspective study saw an ALAL patient failed to respond to the ALL-like treatment recommended in most retrospective studies. However, RNA-seq profiling of this ALAL, together with indepth comparative analysis with AML, ALL and healthy bone marrow samples, demonstrated that the ALAL was transcriptomically more similar to AML, and correspondingly a complete molecular remission (CMR) was achieved with AML-like treatment regimen. Moreover, tracking of transcriptomic profile changes at nine time points throughout the treatment successfully detected tumor relapse seven months earlier than conventional approaches. Under the guidance of this Dynamic Transcriptomic Tracking (DTT) approach, we present a further ALAL patient that reached CMR with an AML-like treatment regimen. DTT maybe beneficial in other leukemias that do not possess recommended treatment guidelines. We propose that DTT is condidered for perspective trials. The direction of treatment for acute leukemia of ambiguous lineage by combining multiple time points sampling and comprehensive transcriptomic similarity analysis