Thrombopoietin is required for full phenotype expression in a JAK2V617F transgenic mouse model of polycythemia vera.

The myeloproliferative neoplasms, polycythemia vera, essential thrombocytosis and primary myelofibrosis are hematopoietic stem cell disorders and share driver mutations that either directly activate the thrombopoietin receptor, MPL, or activate it indirectly through gain-of-function mutations in the gene for JAK2, its cognate tyrosine kinase. Paradoxically, MPL surface expression in hematopoietic stem cells is also reduced in the myeloproliferative neoplasms due to abnormal post-translational glycosylation and premature destruction of JAK2, suggesting that the myeloproliferative neoplasms are disorders of MPL processing since MPL is the only hematopoietic growth factor receptor in hematopoietic stem cells. To examine this possibility, we genetically manipulated MPL expression and maturation in a JAK2V617F transgenic mouse model of polycythemia vera.

Detection of paroxysmal nocturnal hemoglobinuria clones to exclude inherited bone marrow failure syndromes.

Background: Inherited bone marrow failure syndromes (IBMFS) and acquired aplastic anemia (AA) are life-threatening marrow failure disorders. These entities can be difficult to distinguish because they present similarly. Correct diagnosis is imperative for proper therapy.

Metabolomics of colorectal cancer: past and current analytical platforms.

Metabolomics is coming of age as an important area of investigation which may help reveal answers to questions left unanswered or only partially understood from proteomic or genomic approaches. Increased knowledge of the relationship of genes and proteins to smaller biomolecules (metabolites) will advance our ability to diagnose, treat, and perhaps prevent cancer and other diseases that have eluded scientists for generations. Colorectal tumors are the second leading cause of cancer mortality in the USA, and the incidence is rising.

Phase 1 and pharmacokinetic study of bolus-infusion flavopiridol followed by cytosine arabinoside and mitoxantrone for acute leukemias.

Flavopiridol is a protein bound, cytotoxic, cyclin-dependent kinase inhibitor. Flavopiridol given by 1-hour bolus at 50 mg/m(2) daily 3 times followed by cytosine arabinoside and mitoxantrone (FLAM) is active in adults with poor-risk acute leukemias. A pharmacologically derived "hybrid" schedule (30-minute bolus followed by 4-hour infusion) of flavopiridol was more effective than bolus administration in refractory chronic lymphocytic leukemia.

Risk of recurrent stroke in children with sickle cell disease receiving blood transfusion therapy for at least five years after initial stroke.

Objective: To test the hypothesis that children with sickle cell disease (SCD) who have an initial stroke temporally unrelated to another medical event are at higher risk for recurrent stroke than are children who had strokes temporally related to medical events.

Methods: A retrospective cohort study of children with SCD and stroke who received regularly scheduled blood transfusions for a minimum of 5 years was conducted. Medical records were examined for the documentation of antecedent or concurrent medical events (hypertension, acute chest syndrome, aplastic crisis, fever associated with infection, exchange transfusion) associated with physician contact within 14 days before the initial stroke.