Skip to Main Content

Stephanie Massaro, MD, MPH

Associate Professor of Clinical Pediatrics (Hematology/Oncology); Medical Director, Pediatric Hematology/Oncology; Director, Pediatric Palliative Care

Contact Information

Stephanie Massaro, MD, MPH

Mailing Address

  • Pediatric Hematology & Oncology

    PO Box 208064

    New Haven, CT 06520-8064

    United States

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 was 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 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 hypothesized 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.

Coauthors

Research Interests

Cell Differentiation; Leukemoid Reaction; Preleukemia; Hematologic Neoplasms

Selected Publications

Clinical Trials

ConditionsStudy Title
Brain and Nervous System; PediatricsA Phase 3 Randomized Study of Selumetinib Versus Carboplatin/Vincristine in Newly Diagnosed or Previously Untreated Neurofibromatosis Type 1 (NF1) Associated Low-Grade Glioma (LGG)
Brain and Nervous SystemA Phase 3 Randomized Non-Inferiority Study of Carboplatin and Vincristine Versus Selumetinib (NSC# 748727) in Newly Diagnosed or Previously Untreated Low-Grade Glioma (LGG) Not Associated With BRAFV600E Mutations or Systemic Neurofibromatosis Type 1 (NF1)
PediatricsA Phase 3 Randomized Trial for Patients With De Novo AML Comparing Standard Therapy Including Gemtuzumab Ozogamicin (GO) to CPX-351 With GO, and the Addition of the FLT3 Inhibitor Gilteritinib for Patients With FLT3 Mutations
PediatricsPrOspective Non-interventional Study in Patients With Locally Advanced or Metastatic TRK Fusion Cancer Treated With Larotrectinib
Supportive Care; Pediatrics; PreventionStepByStep: A Randomized Trial of a Mobile Health and Social Media Physical Activity Intervention Among Adolescent and Young Adult Childhood Cancer Survivors
Brain and Nervous System; PediatricsA Target Validation/Phase1 Study of BGB-290 in Combination With Temozolomide in Adolescent and Young Adult IDH1/2 Newly Diagnosed and Recurrent Mutant Gliomas
Brain and Nervous System; PediatricsA Phase 2 Study of Dabrafenib (NSC# 763760) With Trametinib (NSC# 763093) After Local Irradiation in Newly-Diagnosed BRAF V600-Mutant High-Grade Glioma (HGG)
Leukemia, not otherwise specified; Leukemia, other; PediatricsA Phase 3 Randomized Trial of Inotuzumab Ozogamicin (NSC#: 772518) for Newly Diagnosed High-Risk B-ALL; Risk-Adapted Post-Induction Therapy for High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and Disseminated B-LLy
PediatricsA Phase 2 Randomized Study of Irinotecan/Temozolomide/Dinutuximab With or Without Eflornithine (DFMO) in Children With Relapsed, Refractory or Progressive Neuroblastoma
Leukemia, not otherwise specified; Leukemia, otherA Phase II Pilot Trial to Estimate Survival After a Non-total Body Irradiation (TBI) Based Conditioning Regimen in Patients Diagnosed With B-acute Lymphoblastic Leukemia (ALL) Who Are Pre-allogeneic Hematopoietic Cell Transplantation (HCT) Next-generation-sequence (NGS) Minimal Residual Disease (MRD) Negative
LiverPediatric Hepatic Malignancy International Therapeutic Trial (PHITT)
Leukemia, not otherwise specified; Leukemia, otherA Phase IB/II Study of Venetoclax (ABT-199) in Combination With Liposomal Vincristine in Patients With Relapsed or Refractory T-Cell or B-Cell Acute Lymphoblastic Leukemia
Brain and Nervous SystemA Phase 3 Study of 131I-Metaiodobenzylguanidine (131I-MIBG) or Crizotinib Added to Intensive Therapy for Children With Newly Diagnosed High-Risk Neuroblastoma (NBL)
Bones and Joints; Kidney; Soft Tissue; PediatricsPhase 3 Accelerated BEP: A Randomised Phase 3 Trial of Accelerated Versus Standard BEP Chemotherapy for Patients With Intermediate and Poor-risk Metastatic Germ Cell Tumors
Soft TissueA Phase 2 Study of Anti-PD-L1 Antibody (Atezolizumab) in Alveolar Soft Part Sarcoma
Lymphoid LeukemiaA Phase 2 Study of the JAK1/JAK2 Inhibitor Ruxolitinib With Chemotherapy in Children With De Novo High-Risk CRLF2-Rearranged and/or JAK Pathway-Mutant Acute Lymphoblastic Leukemia
Bones and Joints; Brain and Nervous System; Eye and Orbit; Hodgkin's Lymphoma; Kidney; Leukemia, other; Liver; Lymphoid Leukemia; Myeloid and Monocytic Leukemia; Non-Hodgkin's Lymphoma; Other Digestive Organ; Other Endocrine System; Other Female Genital; Other Male Genital; Other Respiratory and Intrathoracic Organs; Other Skin; Other Urinary; Ovary; Small Intestine; Soft Tissue; PediatricsThe Project: Every Child Protocol: A Registry, Eligibility Screening, Biology and Outcome Study
Other Respiratory and Intrathoracic Organs; PediatricsEffects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment (HEART)
Brain and Nervous System; PediatricsResponse and Biology-Based Risk Factor-Guided Therapy in Treating Younger Patients With Non-high Risk Neuroblastoma
Brain and Nervous System; PediatricsBiomarkers in Tumor Tissue Samples From Patients With Newly Diagnosed Neuroblastoma or Ganglioneuroblastoma