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Stephanie Massaro, MD, MPH

Associate Professor of Clinical Pediatrics (Hematology/Oncology)

Contact Information

Stephanie Massaro, MD, MPH

Lab Location

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 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.

Coauthors

Research Interests

Cell Differentiation; Leukemoid Reaction; Preleukemia; Hematologic Neoplasms

Selected Publications

Clinical Trials

ConditionsStudy Title
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
StepByStep: A Randomized Trial of a Mobile Health and Social Media Physical Activity Intervention Among Adolescent and Young Adult Childhood Cancer Survivors
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
Leukemia, not otherwise specified; Leukemia, other; PediatricsA Phase III Randomized, Open Label, Multi-center Study of the Safety and Efficacy of Apixaban for Thromboembolism Prevention Versus No Systemic Anticoagulant Prophylaxis During Induction Chemotherapy in Children With Newly Diagnosed Acute Lymphoblastic Leukemia (ALL) or Lymphoma (T or B Cell) Treated With Asparaginase
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)
Other Hematopoietic; PediatricsThe Effectiveness of Lactobacillus Plantarum (LBP) in Preventing Acute Graft-Versus-Host Disease (GvHD) in Children Undergoing Alternative Hematopoietic Progenitor Cell Transplantation (HCT)
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
Hodgkin's LymphomaA Phase III, Randomized Study of Nivolumab (Opdivo) Plus AVD or Brentuximab Vedotin (Adcetris) Plus AVD in Patients (Age >/= 12 Years) With Newly Diagnosed Advanced Stage Classical Hodgkin Lymphoma
Hodgkin's LymphomaAn Open-label, Uncontrolled, Multicenter Phase II Trial of MK-3475 (Pembrolizumab) in Children and Young Adults With Newly Diagnosed Classical Hodgkin Lymphoma With Inadequate (Slow Early) Response to Frontline Chemotherapy (KEYNOTE 667)
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
Leukemia, other; PediatricsA Phase 3 Trial Investigating Blinatumomab ( NSC# 765986) in Combination With Chemotherapy in Patients With Newly Diagnosed Standard Risk or Down Syndrome B-Lymphoblastic Leukemia (B-ALL) and the Treatment of Patients With Localized B-Lymphoblastic Lymphoma (B-LLy)
LiverPediatric Hepatic Malignancy International Therapeutic Trial (PHITT)
Lymphoid LeukemiaA 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
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
Bones and Joints; Brain and Nervous System; Leukemia, not otherwise specified; Leukemia, other; Lymphoid LeukemiaNCI-COG Pediatric MATCH (Molecular Analysis for Therapy Choice) Screening Protocol
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
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 BladderA 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)
Brain and Nervous System; PediatricsA Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma