Splenic complications in pediatric sickle cell disease: A retrospective cohort review.

Objective: To delineate the natural history of splenic complications other than loss of splenic function in children with sickle cell disease (SCD), we performed a retrospective chart review of patients with SCD treated at the Texas Children's Hospital.

Methods: We determined the dates of diagnoses of splenic complications, the number of acute splenic sequestration crises (ASSC), and hydroxyurea treatment in pediatric patients with SCD. We also examined the association of hydroxyurea therapy with the onset and severity of ASSC.

Dose-dependent effects of Dnmt3a in an inducible murine model of Kras-driven leukemia.

DNMT3A mutations are frequently found in clonal hematopoiesis and a variety of hematologic malignancies, including acute myeloid leukemia. An assortment of mouse models have been engineered to explore the tumorigenic potential and malignant lineage bias due to loss of function of DNMT3A in consort with commonly comutated genes in myeloid malignancies, such as Flt3, Nras, Kras, and c-Kit. We employed several tamoxifen-inducible Cre-ER murine model systems to study the effects of constitutively active Kras-driven myeloid leukemia (Kras) development together with heterozygous (3aHet) or homozygous Dnmt3a deletion (3aKO).

Cohesin Subunit RAD21 Regulates the Differentiation and Self-Renewal of Hematopoietic Stem and Progenitor Cells.

Recent studies suggest that chromosomal cohesin complex proteins are important in regulating hematopoiesis and may contribute to myeloid malignancies. To investigate the effects of perturbing the cohesin subunit protein RAD21 on normal hematopoiesis, we used conditional knockout (cKO) mouse models. While cohesin is vital for hematopoietic stem cell (HSC) function, Rad21 haploinsufficiency (Rad21Δ/+) led to distinct hematopoietic phenotypes.

Management of Acute Promyelocytic Leukemia at Extremes of Age.

Tailored treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has revolutionized the outcome of acute promyelocytic leukemia (APL) from a uniformly fatal disease to one of the most curable malignant diseases in humans. Due to its high efficacy, ATO/ATRA is the standard first-line therapy in younger adult, non-high-risk APL patients. However, early death is still a major issue in APL, particularly in older patients.

Corrigendum: Murine models of acute myeloid leukemia.

[This corrects the article DOI: 10.3389/fonc.2022.

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.

Association of race and ethnicity with clinical phenotype, genetics, and survival in pediatric acute myeloid leukemia.

Black and Hispanic children with acute myeloid leukemia (AML) have worse outcomes compared with White children. AML is a heterogeneous disease with numerous genetic subtypes in which these disparities have not been specifically investigated. In this study, we used the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database to examine the association of race-ethnicity with leukemia cytogenetics, clinical features, and survival outcomes within major cytogenetic subgroups of pediatric AML.

Modeling IKZF1 lesions in B-ALL reveals distinct chemosensitivity patterns and potential therapeutic vulnerabilities.

IKAROS family zinc finger 1 (IKZF1) alterations represent a diverse group of genetic lesions that are associated with an increased risk of relapse in B-cell acute lymphoblastic leukemia. Due to the heterogeneity of concomitant lesions, it remains unclear how IKZF1 abnormalities directly affect cell function and therapy resistance, and whether their consideration as a prognostic indicator is valuable in improving outcome. CRISPR/Cas9 strategies were used to engineer multiple panels of isogeneic lymphoid leukemia cell lines with a spectrum of IKZF1 lesions to measure changes in chemosensitivity, gene expression, cell cycle, and in vivo engraftment that can be linked to loss of IKAROS protein.

Perturbed hematopoiesis in individuals with germline DNMT3A overgrowth Tatton-Brown-Rahman syndrome.

Tatton-Brown-Rahman syndrome (TBRS) is an overgrowth disorder caused by germline heterozygous mutations in the DNA methyltransferase DNMT3A. DNMT3A is a critical regulator of hematopoietic stem cell (HSC) differentiation and somatic DNMT3A mutations are frequent in hematologic malignancies and clonal hematopoiesis. Yet, the impact of constitutive DNMT3A mutation on hematopoiesis in TBRS is undefined.

Acute Myeloid Leukemia in Children: Emerging Paradigms in Genetics and New Approaches to Therapy.

Purpose Of Review: Acute myeloid leukemia (AML) in children remains a challenging disease to cure with suboptimal outcomes particularly when compared to the more common lymphoid leukemias. Recent advances in the genetic characterization of AML have enhanced understanding of individualized patient risk, which has also led to the development of new therapeutic strategies. Here, we review key cytogenetic and molecular features of pediatric AML and how new therapies are being used to improve outcomes.

Use of Allopurinol to Mitigate 6-Mercaptopurine Associated Gastrointestinal Toxicity in Acute Lymphoblastic Leukemia.

An essential component of acute lymphoblastic leukemia (ALL) therapy is the prolonged maintenance phase with daily 6-mercaptopurine (6-MP) as the cornerstone. While 6-MP is generally well-tolerated, some patients suffer from significant side effects such as gastrointestinal (GI) toxicity, including hepatitis, hypoglycemia, nausea, and pancreatitis, which can substantially limit the tolerated dose of 6-MP. These toxicities are thought to result from skewed metabolism of 6-MP leading to an accumulation of the 6-methylmercaptopurine (6-MMP) metabolite.

Advances in Pediatric Acute Promyelocytic Leukemia.

Acute promyelocytic leukemia (APL) is a rare disease accounting for only 5%-10% of pediatric acute myeloid leukemia (AML) and fewer than 1000 cases occur annually in the United States across all age groups. Characterized by t (15; 17), with a resultant gene fusion driving leukemia development, advances in therapy have improved outcomes for APL significantly in the past several decades, now making APL the most curable form of AML in both children and adults. Cure rates in APL are now comparable to pediatric B-lymphoid leukemias.

The genomics of acute myeloid leukemia in children.

Acute myeloid leukemia (AML) is a clinically, morphologically, and genetically heterogeneous disorder. Like many malignancies, the genomic landscape of pediatric AML has been mapped recently through sequencing of large cohorts of patients. Much has been learned about the biology of AML through studies of specific recurrent genetic lesions.

Decreasing Duration of Antibiotic Prescribing for Uncomplicated Skin and Soft Tissue Infections.

Background And Objective: Short courses of antibiotics are often indicated for uncomplicated skin and soft tissue infections (uSSTIs). Our objective was to decrease duration of antibiotics prescribed in children hospitalized for uSSTIs by using quality improvement (QI) methods.

Methods: QI methods were used to decrease duration of antibiotics prescribed upon hospital discharge for uSSTIs.