Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia.

Acute myeloid leukemia (AML) microenvironment exhibits cellular and molecular differences among various subtypes. Here, we utilize single-cell RNA sequencing (scRNA-seq) to analyze pediatric AML bone marrow (BM) samples from diagnosis (Dx), end of induction (EOI), and relapse timepoints. Analysis of Dx, EOI scRNA-seq, and TARGET AML RNA-seq datasets reveals an AML blasts-associated 7-gene signature (CLEC11A, PRAME, AZU1, NREP, ARMH1, C1QBP, TRH), which we validate on independent datasets.

Pediatric T-cell acute lymphoblastic leukemia blast signature and MRD associated immune environment changes defined by single cell transcriptomics analysis.

Different driver mutations and/or chromosomal aberrations and dysregulated signaling interactions between leukemia cells and the immune microenvironment have been implicated in the development of T-cell acute lymphoblastic leukemia (T-ALL). To better understand changes in the bone marrow microenvironment and signaling pathways in pediatric T-ALL, bone marrows collected at diagnosis (Dx) and end of induction therapy (EOI) from 11 patients at a single center were profiled by single cell transcriptomics (10 Dx, 5 paired EOI, 1 relapse). T-ALL blasts were identified by comparison with healthy bone marrow cells.

Molecular Evolution of Classic Hodgkin Lymphoma Revealed Through Whole-Genome Sequencing of Hodgkin and Reed Sternberg Cells.

Unlabelled: The rarity of malignant Hodgkin and Reed Sternberg (HRS) cells in classic Hodgkin lymphoma (cHL) limits the ability to study the genomics of cHL. To circumvent this, our group has previously optimized fluorescence-activated cell sorting to purify HRS cells. Using this approach, we now report the whole-genome sequencing landscape of HRS cells and reconstruct the chronology and likely etiology of pathogenic events leading to cHL.

Pathologic mechanobiological interactions between red blood cells and endothelial cells directly induce vasculopathy in iron deficiency anemia.

The correlation between cardiovascular disease and iron deficiency anemia (IDA) is well documented but poorly understood. Using a multi-disciplinary approach, we explore the hypothesis that the biophysical alterations of red blood cells (RBCs) in IDA, such as variable degrees of microcytosis and decreased deformability may directly induce endothelial dysfunction via mechanobiological mechanisms. Using a combination of atomic force microscopy and microfluidics, we observed that subpopulations of IDA RBCs (idRBCs) are significantly stiffer and smaller than both healthy RBCs and the remaining idRBC population.

Comparison of Mid-turbinate Nasal Swabs, Saliva, and Nasopharyngeal Swabs for SARS-CoV-2 Reverse Transcription-Polymerase Chain Reaction Testing in Pediatric Outpatients.

Context.—: Diagnostic testing for SARS-CoV-2 in symptomatic and asymptomatic children remains integral to care, particularly for supporting return to and attendance in schools. The concordance of SARS-CoV-2 detection in children, using various specimen types, has not been widely studied.

Clonal Evolution of B-Cell Acute Lymphoblastic Leukemia with del(9)(p13p21) into Mixed Phenotype Acute Leukemia Presenting as an Isolated Testicular Relapse.

Lineage switch in acute leukemias is a well-reported occurrence; however, most of these cases involve a switch from either lymphoid to myeloid or myeloid to lymphoid lineage. Here, we report a case of a 14-year-old male with B-cell acute lymphoblastic leukemia (B-ALL) who initially responded well to standard chemotherapy but then later developed mixed phenotype acute leukemia (MPAL) at relapse, likely reflecting a clonal evolution of the original leukemia with a partial phenotypic shift. The patient had a del(9)(p13p21) in his leukemia blasts at diagnosis, and the deletion persisted at relapse along with multiple additional cytogenetic aberrations.

Hemophagocytic Lymphohistiocytosis Secondary to T Cell/Histiocyte-rich Large B Cell Lymphoma in an Adolescent Male.

Hemophagocytic Lymphohistiocytosis (HLH) is a hyperinflammatory disorder that may be encountered as a primary or secondary phenomenon. HLH secondary to lymphoma has been described, more frequently in adults than in children. T-cell/Histiocyte-rich B-cell lymphoma (THRLBCL) is a large B-cell lymphoma that resides in a microenvironment of robust host immune response and has previously been associated with HLH in adults.

CD36-positive B-lymphoblasts Predict Poor Outcome in Children With B-lymphoblastic Leukemia.

Objective We observed that pediatric patients with B lymphoblastic leukemia which expressed CD36 at diagnosis seemed to have worse outcome than patients whose blasts did not. Here, we describe the patient, disease characteristics, pathological, molecular, and genetic features and outcomes of patients with CD36+ B-LL compared to patients with CD36- B-LL. Methods We retrospectively reviewed all flow cytometry reports from September 2008 to December 2015 to identify patients diagnosed at our institution with CD36 expression on B lymphoblasts.

Concurrent myeloid sarcoma, atypical teratoid/rhabdoid tumor, and hypereosinophilia in an infant with a germline SMARCB1 mutation.

We report a 1-year-old female child presenting with hypereosinophilia who was found to have concurrent myeloid sarcoma and a central nervous system (CNS) atypical teratoid/rhabdoid tumor (AT/RT). She was later found to have a germline mutation in SMARCB1. Concurrent hematologic malignancy and CNS AT/RT have not previously been described in the context of a SMARCB1 loss-of-function germline mutation.

Atypical Marginal Zone Hyperplasia Is a Mimic for Lymphoma in Pediatric Transplant Recipients: Report of Two Patients.

Atypical marginal zone hyperplasia (AMZH) of mucosa-associated lymphoid tissue (MALT) closely resembles lymphoma in that it shows expansion of the marginal zones with prominent intraepithelial B lymphocytes, is immunoglobulin light-chain restricted, and may show aberrant CD43 expression. However, unlike lymphoma, it does not show rearrangement of the immunoglobulin heavy chain gene (immunoglobulin H [IgH]) by polymerase chain reaction (PCR), and it behaves in a benign fashion. We identified AMZH in 2 pediatric solid organ transplant recipients who presented with adenotonsillar hypertrophy.

Monocytopenia as a diagnostic clue to pediatric B-lymphoblastic leukemia with rare circulating blasts.

B-lymphoblastic leukemia/lymphoma (B-LL) is the most common childhood cancer. Circulating blasts in the peripheral blood may be rare (≤1%) and missed, even when flow cytometric immunophenotyping is performed, leading to a false-negative report. The records from all patients with a new diagnosis of B-LL between January 2009 and December 2011 at our institution were reviewed.

Monocytopenia as a diagnostic clue to pediatric B-lymphoblastic leukemia with rare circulating blasts.

Abstract Background: B-lymphoblastic leukemia/lymphoma (B-LL) is the most common childhood cancer. Occasionally, circulating blasts in the peripheral blood are rare ({less than or equal to}1%) and may be missed, even when flow cytometric immunophenotyping is performed, leading to a false negative report. Methods: The records from all patients with a new diagnosis of B-LL at our institution were reviewed from Jan 2009-Dec 2011.