Peter D. Emanuel
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View article: Juvenile myelomonocytic leukemia stem cells are sensitive to NK cell–mediated lysis and express targetable antigens
Juvenile myelomonocytic leukemia stem cells are sensitive to NK cell–mediated lysis and express targetable antigens Open
Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm for which hematopoietic stem cell transplantation is the only curative treatment. Innovative therapies are needed to address high rates of morbidity, treatment-relate…
View article: Progressive dyspnoea in a rare disease – clinical case
Progressive dyspnoea in a rare disease – clinical case Open
Pulmonary alveolar proteinosis (PAP) is a rare entity characterised by dysfunction of alveolar macrophages, concomitant with accumulation of surfactant (phospholipoprotein material) in the alveolar space, without inflammatory infiltration …
View article: The genomic landscape of juvenile myelomonocytic leukemia
The genomic landscape of juvenile myelomonocytic leukemia Open
Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative neoplasm (MPN) of childhood with a poor prognosis. Mutations in NF1, NRAS, KRAS, PTPN11 and CBL occur in 85% of patients, yet there are currently no risk stratification algori…
View article: Sustained fetal hematopoiesis causes juvenile death from leukemia: evidence from a dual-age–specific mouse model
Sustained fetal hematopoiesis causes juvenile death from leukemia: evidence from a dual-age–specific mouse model Open
It is not clear whether disrupted age-specific hematopoiesis contributes to the complex manifestations in leukemia patients who carry identical mutations, particularly in pediatric and adult patients with similar clinical characteristics. …
View article: M1 and M2 macrophages differentially regulate hematopoietic stem cell self-renewal and ex vivo expansion
M1 and M2 macrophages differentially regulate hematopoietic stem cell self-renewal and ex vivo expansion Open
Key Points M2-MΦs promote and M1-MΦs inhibit HSC self-renewal via differential expression of Arg1 and NOS2, respectively. Coculture of hUCB CD34+ cells with M2-MΦs resulted in a significant expansion of CD34+ cells and SCID–mice repopulati…
View article: Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects
Targeting tumor-associated carbohydrate antigens: a phase I study of a carbohydrate mimetic-peptide vaccine in stage IV breast cancer subjects Open
Tumor-associated carbohydrate antigens (TACAs) support cell survival that could be interrupted by anti-TACA antibodies. Among TACAs that mediate cell survival signals are the neolactoseries antigen Lewis Y (LeY) and the ganglioside GD2. To…
View article: Managing Expectations in the Transition to Proof of Concept Studies
Managing Expectations in the Transition to Proof of Concept Studies Open
The old paradigm considers patients equal with similar chances to respond to treatments, but the new paradigm considers patient's heterogeneity, a major fact that informs the design of clinical trials. By linking every treatment to a mecha…
View article: Fludarabine, Melphalan, and Alemtuzumab Conditioning Regimen in High Risk Leukemia: The Arkansas Experience
Fludarabine, Melphalan, and Alemtuzumab Conditioning Regimen in High Risk Leukemia: The Arkansas Experience Open
Introduction: Fludarabine, melphalan and alemtuzumab (Campath) [FMC] based reduced intensity conditioning (RIC) regimen has been promising with lower incidence of acute/chronic GVHD and comparable non-relapse mortality (NRM) rate. The Arka…
View article: Timing of the loss of Pten protein determines disease severity in a mouse model of myeloid malignancy
Timing of the loss of Pten protein determines disease severity in a mouse model of myeloid malignancy Open
Key Points Early postnatal loss of Pten protein in mice with Nf1 haploinsufficiency causes a fatal juvenile myeloproliferative neoplasm. Akt and MAPK activities are elevated in juvenile mice with Nf1 haploinsufficiency and Pten protein los…