Stephanie A Massaro, MD, MPH

Clinician in Pediatrics (Hematology / Oncology)

Research Interests

Cell Differentiation; Leukemoid Reaction; Preleukemia; Hematologic Neoplasms

Research Organizations

Pediatrics: Pediatric Hematology & Oncology

Yale Cancer Center

Research Summary

Acute Megakaryoblastic Leukemia (AMKL) is a rare form of pediatric leukemia that affects megakaryocytes, which are platelet-making blood cells.  The disease most commonly strikes very young children and is associated with an extremely poor outcome with an average survival time of only eight months from diagnosis despite aggressive medical therapy.   Approximately 30% of pediatric patients diagnosed with AMKL are infants who have a specific genetic abnormality that involves two genes, RBM15 and MKL1.  These genes may play important roles in normal blood cell development.  However, when they are incorrectly linked together, they may contribute to leukemia. The focus of my research is to identify the mechanisms underlying the development of AMKL.  

Extensive Research Description

Acute Megakaryoblastic Leukemia (AMKL) is a rare form of pediatric leukemia that disproportionately affects children.  AMKL associated with the chromosomal translocation fusing RNA Binding Motif 15 gene (RBM15) on chromosome 1 upstream of the transcriptional cofactor Megakaryoblastic Leukemia 1 gene (MKL1) on chromosome 22 (t1;22), is most commonly diagnosed in infants less than three months of age and requires aggressive medical management. Thus, it is likely that the leukemia originates in utero when the hematopoietic system is in its embryonic or fetal stages. We have successfully recapitulated megkaryopoiesis in vitro using human embryonic stem cells and established a model system in which to study megakaryocyte differentiation.  Human embryonic stem cells (hESCs) offer a mechanism to study embryogenesis and to understand the processes of fetal blood maturation and leukemia development. We seek to further define the roles of MKL1 and RBM15 during hESC-derived megakaryopoiesis.  Furthermore, we hypothesize that the fusion product (RBM15-MKL1) promotes the leukemic phenotype by causing aberrant Notch signaling and subsequent derangement of the RB tumor suppressor pathway. We are currently studying the interactions of RBM15,MKL1 and RBM15-MKL1, with regulators of cell growth and differentiation during megakaryocyte development using both primary AMKL patient samples and this in vitro model of developmental hematopoieisis.  

Selected Publications

Edit this profile

Contact Info

Stephanie A Massaro, MD, MPH
Patient Care Location
Yale Pediatric Hematology/OncologySmilow Cancer Hospital at Yale New Haven
35 Park Street, Ste 7th floor

New Haven, CT 06511
View on map...
Lab Location
Amistad Street Building
10 Amistad Street, Ste 214

New Haven, CT 06519
View on map...
Mailing Address
Pediatric Hematology & OncologyPO Box 208064
New Haven, CT 06520-8064

Curriculum Vitae

The Krause Laboratory