Notable Publications

Pediatric acute myeloid leukemia (AML) is a rare disease with roughly 500 cases diagnosed in the United States each year and has had minimal improvement in clinical outcomes over recent decades. Novel treatment development to improve outcomes may be enhanced with an accompanying test for predicting treatment response.

Approximately 50% of acute myeloid leukemia (AML) patients do not respond to induction therapy (primary induction failure [PIF]) or relapse after <6 months (early relapse [ER]).

Precision medicine approaches such as ex vivo drug sensitivity screening (DSS) are appealing to inform rational drug selection in myelodysplastic syndromes (MDSs) and acute myeloid leukemia, given their marked biologic heterogeneity.

A cryptic inv(16)(p13.3q24.3) encoding the CBFA2T3-GLIS2 fusion is associated with poor outcome in infants with acute megakaryocytic leukemia. We aimed to broaden our understanding of the pathogenesis of this fusion through transcriptome profiling.

Prognoses for acute promyelocytic leukemia (APL) patients improved drastically upon the introduction of differentiation therapy with all-trans-retinoic acid (ATRA) in combination with conventional chemotherapy. Unfortunately, this therapeutic approach has not translated to other genetic subtypes of acute myeloid leukemia...

To identify cancer cell types that are sensitive to PTC299, a panel of 240 tumor cell lines was tested against which the concentration of compound required to reduce cell viability by 50% (CC50) was determined. Overall, the viability of 18% of cells from solid tumor(34/184) and ~57% of cells from hematologic malignancies (32/56) was reduced...

The barcodes were then used to reassemble the genetic profiles of cells from next-generation sequencing data. We applied this approach to sequential clinical MDS samples, genotyping the most clinically relevant loci across more than 15,000 individual cells. Additionally, to study effects of subclonal mutations on drug sensitivity, ex vivo functional...

Myelodysplastic syndromes (MDS) are a collection of clonal diseases of dysfunctional hematopoietic stem cells, characterized by ineffective hematopoiesis, cytopenias, and dysplasia. Limited conventional treatment options exist for these patients, with hypomethylating agents remaining the standard of care for higher-risk MDS patients.

The clinical heterogeneity of the myelodysplastic syndromes (MDSs) relates to the recently discerned panoply of molecular abnormalities extant within this disease spectrum. Despite increasing recognition of these biologic abnormalities, very limited therapeutic options exist to exploit our increasing understanding of the molecular pathophysiology of MDS.

We performed drug sensitivity profiling on 60 patient samples in both newly diagnosed and treatment-refractory myeloid neoplasms (46 MDS, 4 CMML, 10 AML). Fresh bone marrow aspirates and/or peripheral blood specimens were RBC-lysed and re-suspended in serum-free media with cytokines.