Stephanie Massaro, MD, MPH

Assistant Professor of Clinical Pediatrics (Hematology/Oncology)

Research Departments & Organizations

Pediatrics: Pediatric Hematology & Oncology

Yale Cancer Center

Research Interests

Cell Differentiation; Hematologic Neoplasms; Leukemoid Reaction; Preleukemia

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.  

Clinical Trials

Conditions Study Title
Brain and Nervous System A Phase 2 Study of Veliparib (ABT-888) and Local Irradiation, Followed by Maintenance Veliparib and Temozolomide, in Patients With Newly Diagnosed High-Grade Glioma (HGG) Without H3 K27M or BRAFV600E Mutations
Lymphoid Leukemia A Phase 1 Study of Blinatumomab in Combination With Checkpoint Inhibitor(s) of PD-1 (Nivolumab) or Both PD-1 (Nivolumab) and CTLA-4 (Ipilimumab) in Patients With Poor-Risk, Relapsed or Refractory CD19+ Precursor B-Lymphoblastic Leukemia
Brain and Nervous System A 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, Pediatrics Phase 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
Pediatrics Phase 2 Trial of XL184 (Cabozantinib) an Oral Small-Molecule Inhibitor of Multiple Kinases, in Children and Young Adults With Refractory Sarcomas, Wilms Tumor, and Other Rare Tumors
Pediatrics A Phase 1/2 Study of VX15/2503 in Children, Adolescents, or Young Adults With Recurrent or Relapsed Solid Tumors
Bones and Joints, Brain and Nervous System, Leukemia, not otherwise specified, Leukemia, other, Lymphoid Leukemia NCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) Screening Protocol
Lymphoid Leukemia A 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
Hodgkin's Lymphoma, Pediatrics Risk-based, Response-adapted, Phase II Open-label Trial of Nivolumab + Brentuximab Vedotin (N + Bv) for Children, Adolescents, and Young Adults With Relapsed/Refractory (R/R) CD30 + Classic Hodgkin Lymphoma (cHL) After Failure of First-line Therapy, Followed by Brentuximab + Bendamustine (Bv + B) for Participants With a Suboptimal Response (CheckMate 744: CHECKpoint Pathway and Nivolumab Clinical Trial Evaluation)
Anus, Breast - Female, Breast - Male, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung, Melanoma, skin, Other Digestive Organ, Other Endocrine System, Other Female Genital, Other Male Genital, Other Respiratory and Intrathoracic Organs, Other Skin, Other Urinary, Ovary, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Pediatrics, Cervix, Urinary Bladder A Randomized Phase 3 Study of Vincristine, Dactinomycin, Cyclophosphamide (VAC) Alternating With Vincristine and Irinotecan (VI) Versus VAC/VI Plus Temsirolimus (TORI, Torisel, NSC# 683864) in Patients With Intermediate Risk (IR) Rhabdomyosarcoma (RMS)
Other Male Genital, Ovary Active Surveillance, Bleomycin, Carboplatin, Etoposide, or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
Anus, Bones and Joints, Brain and Nervous System, Breast - Female, Breast - Male, Colon, Corpus Uteri, Esophagus, Eye and Orbit, Hodgkin's Lymphoma, Kaposi's sarcoma, Kidney, Larynx, Lip, Oral Cavity and Pharynx, Liver, Lung, Melanoma, skin, Mycosis Fungoides, 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, Pancreas, Prostate, Rectum, Small Intestine, Soft Tissue, Stomach, Thyroid, Pediatrics, Cervix, Urinary Bladder A Phase I/II Study of Pembrolizumab (MK-3475) in Children With Advanced Melanoma or a PD-L1 Positive Advanced, Relapsed or Refractory Solid Tumor or Lymphoma (KEYNOTE-051)
Brain and Nervous System, Pediatrics A Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma
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, Pediatrics The Project: Every Child Protocol: A Registry, Eligibility Screening, Biology and Outcome Study
Other Respiratory and Intrathoracic Organs, Pediatrics Effects of Dexrazoxane Hydrochloride on Biomarkers Associated With Cardiomyopathy and Heart Failure After Cancer Treatment (HEART)
Brain and Nervous System, Pediatrics Response and Biology-Based Risk Factor-Guided Therapy in Treating Younger Patients With Non-high Risk Neuroblastoma
Brain and Nervous System, Pediatrics Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Younger Patients With Newly Diagnosed Ependymoma
Brain and Nervous System, Pediatrics Biomarkers in Tumor Tissue Samples From Patients With Newly Diagnosed Neuroblastoma or Ganglioneuroblastoma
Lymphoid Leukemia, Pediatrics Neuropsychological and Behavioral Testing in Younger Patients With Cancer
Leukemia, not otherwise specified, Pediatrics Risk-Stratified Randomized Phase III Testing of Blinatumomab in First Relapse of Childhood B-Lymphoblastic Leukemia (B-ALL)

Selected Publications

  • Role for MKL1 in megakaryocytic maturation.

    Cheng EC, Luo Q, Bruscia EM, Renda MJ, Troy JA, Massaro SA, Tuck D, Schulz V, Mane SM, Berliner N, Sun Y, Morris SW, Qiu C, Krause DS. Role for MKL1 in megakaryocytic maturation. Blood 2009, 113:2826-34. 2009

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Contact Info

Stephanie Massaro, MD, MPH
Lab Location
Amistad Street Building
10 Amistad Street, Ste 214

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

Curriculum Vitae

The Krause Laboratory