Near-Haploid B-Cell Acute Lymphoblastic Leukemia in a Patient with Rubinstein-Taybi Syndrome.

Rubinstein-Taybi syndrome (RSTS) is a rare disorder characterized by developmental delay, short stature, dysmorphic facies and skeletal abnormalities. RSTS has been linked to a variety of malignant and benign tumors, but the frequency and characteristics of RSTS-related neoplasms remain unclear. We describe a unique case of near haploid B-cell lymphoblastic leukemia (B-ALL) in a 6-year-old girl with RSTS who harbors a likely pathogenic variant in CREBBP. Somatic CREBBP variants are enriched in some subsets of ALL; however, germline variants have not been previously described in childhood leukemia and may represent an underrecognized predisposition to malignancy. Our patient's disease responded poorly to conventional chemotherapy and relapsed following a complete remission achieved with CD19 CAR T cell therapy. We propose that the constitutional CREBBP variant may have played a significant role in the leukemia's resistance to chemotherapy and this patient's poor response to therapy.

Improving Outcomes for Children Requiring Extracorporeal Membrane Oxygenation Therapy Following Hematopoietic Stem Cell Transplantation.

OBJECTIVES: The objective of this study was to provide an updated review of survival for pediatric hematopoietic stem cell transplantation patients requiring extracorporeal membrane oxygenation therapy as well as characterize the demographics, clinical variables, and complications associated with mortality. DESIGN: Retrospective database review of the Extracorporeal Life Support Organization Registry from 1990 to 2019. SETTING: Extracorporeal membrane oxygenation centers reporting to Extracorporeal Life Support Organization. PATIENTS: Patients treated with extracorporeal membrane oxygenation greater than 28 days to 18 years old with International Classification of Diseases Ninth Revision, International Classification of Diseases Tenth Revision, and current procedural terminology codes consistent with hematopoietic stem cell transplantation were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographics, year of extracorporeal membrane oxygenation run, clinical variables, comorbid diagnoses, and extracorporeal membrane oxygenation complications were assessed in relation to the primary study outcome of survival to hospital discharge. Ninety patients were included in the final analysis. The overall survival rate for the study period was 19%. However, the survival rate in the last decade (2010-2019) improved to 26% (p = 0.01; odds ratio 9.4 [1.2-74.8]). Factors associated with decreased survival included comorbid malignancy, elevated peak inspiratory pressure in conventionally ventilated patients, and pulmonary and metabolic complications on extracorporeal membrane oxygenation. CONCLUSIONS: Pediatric patients posthematopoietic stem cell transplantation supported with extracorporeal membrane oxygenation have improving survival rates over time. With 26% of patients (16/62) surviving to hospital discharge in the last decade (2010-2019), history of hematopoietic stem cell transplantation may no longer be considered an absolute contraindication to extracorporeal membrane oxygenation. As advancements are made in hematopoietic stem cell transplantation therapies and extracorporeal membrane oxygenation management, the indications for life-saving extracorporeal membrane oxygenation support among patients posthematopoietic stem cell transplantation may expand accordingly.

Murine Models of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a phenotypically and genetically heterogeneous hematologic malignancy. Extensive sequencing efforts have mapped the genomic landscape of adult and pediatric AML revealing a number of biologically and prognostically relevant driver lesions. Beyond identifying recurrent genetic aberrations, it is of critical importance to fully delineate the complex mechanisms by which they contribute to the initiation and evolution of disease to ultimately facilitate the development of targeted therapies. Towards these aims, murine models of AML are indispensable research tools. The rapid evolution of genetic engineering techniques over the past 20 years has greatly advanced the use of murine models to mirror specific genetic subtypes of human AML, define cell-intrinsic and extrinsic disease mechanisms, study the interaction between co-occurring genetic lesions, and test novel therapeutic approaches. This review summarizes the mouse model systems that have been developed to recapitulate the most common genomic subtypes of AML. We will discuss the strengths and weaknesses of varying modeling strategies, highlight major discoveries emanating from these model systems, and outline future opportunities to leverage emerging technologies for mechanistic and preclinical investigations.

Corrigendum: Murine models of acute myeloid leukemia.

[This corrects the article DOI: 10.3389/fonc.2022.854973.].