A 59-year-old man with lung cancer, peripheral blood leukocytosis and thrombocytosis without peripheral lymphadenopathy and hepatosplenomegaly was found to have pancreatic extramedullary hematopoiesis (EMH) in association with an 'atypical' myeloproliferative disorder. Studies for the Philadelphia chromosome and bcr-abl fusion product were negative. This is the first documented case in the literature of isolated EMH in the pancreas.

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Blood cells are continuously produced throughout our lifetime by a rare pluripotent cell that primarily resides in the adult bone marrow. This hematopoietic stem cell (HSC) must maintain a careful balance between self-renewal, differentiation and apoptosis in order to support hematopoiesis for such a long duration. Understanding the mechanism of balance between these fates is crucial to our understanding and clinical application of these cells. From previous studies, we know Src homology 2 domain containing 5' inositol phosphatase 1 (SHIP) plays an important role in HSC homeostasis and function. Most interestingly SHIP impacts HSC homing to the bone marrow niche. An ideal location and environment is essential for HSC to fulfill their physiological roles. Here we present evidence that SHIP is expressed by cells of the HSC niche. Furthermore, SHIP deficiency severely alters this environment and thus damages HSC function. In addition to the extrinsic effects of a SHIP-deficient microenvironment on HSC, there is an intrinsic requirement for SHIP expression in confining HSC to the bone marrow niche. We previously demonstrated that lack of SHIP leads to an increase in peripheral HSC. Here we demonstrate that SHIP-deficient HSC from the spleen can provide radioprotection and sustained multi-lineage repopulation in lethally irradiated hosts. This indicates extramedullary HSC can function outside the traditional bone marrow niche in SHIP-deficient mice. Combined, these studies indicate both extrinsic and intrinsic factors contribute to HSC homeostasis and function. In order to better understand the signaling pathways involved in self-renewal and differentiation, we applied an array-based technology to hematopoietic cells at various levels of differentiation. Comparing the phosphorylation signature, or 'kinome', of these cell types can help pinpoint signaling mechanisms important for HSC self-renewal and lineage commitment.

β-thalassemia is an autosomal recessive blood disease caused by mutations in β-globin genes that either reduce or altogether abolish β-globin chain synthesis. Normally, two β-globin chains would combine with two α-globin chains and a heme group to form hemoglobin. Because α-globin chain synthesis is unaffected in β-thalassemia patients, the unpaired α-globin chains accumulate and precipitate. The reduced formation of hemoglobin and accumulation of unpaired α-globin chains are the two fundamental molecular pathologies. In the most serious cases of the disease, the resulting complications develop before two years of age. Most often, these include severe anemia, pallor, jaundice, abdominal enlargement, and distinct craniofacial features. If left untreated, the disease is fatal before the age of three in the most serious cases. Each year, more than 40,000 births, mostly in Southeast Asia, Middle East, or Africa, are affected with β-thalassemia. With increased migration, however, β-thalassemia is becoming more common in Europe and North America. Currently, the most widespread treatment for the disease is transfusions and iron chelation therapy, and the only cure is hematopoietic stem cell transplantation. In recent years, however, multiple treatments and potential cures such as fetal hemoglobin inducers and gene therapy have shown promise. By analyzing the cost-efficiency, viability, and therapeutic benefits of current and future treatments, it can be seen that a combination of fetal hemoglobin inducers, transfusions, and iron chelation therapy will have the greatest impact for the vast majority of β-thalassemia patients.

Background: Extramedullary manifestations (EM) are rare in acute myeloid leukemia (AML) and their impact on clinical outcomes is controversially discussed. - Methods: We retrospectively analyzed a large multi-center cohort of 1583 newly diagnosed AML patients, of whom 225 (14.21%) had EM. - Results: AML patients with EM presented with significantly higher counts of white blood cells (p < 0.0001), peripheral blood blasts (p < 0.0001), bone marrow blasts (p = 0.019), and LDH (p < 0.0001). Regarding molecular genetics, EM AML was associated with mutations of NPM1 (OR: 1.66, p < 0.001), FLT3-ITD (OR: 1.72, p < 0.001) and PTPN11 (OR: 2.46, p < 0.001). With regard to clinical outcomes, EM AML patients were less likely to achieve complete remissions (OR: 0.62, p = 0.004), and had a higher early death rate (OR: 2.23, p = 0.003). Multivariable analysis revealed EM as an independent risk factor for reduced overall survival (hazard ratio [HR]: 1.43, p < 0.001), however, for patients who received allogeneic hematopoietic cell transplantation (HCT) survival did not differ. For patients bearing EM AML, multivariable analysis unveiled mutated TP53 and IKZF1 as independent risk factors for reduced event-free (HR: 4.45, p < 0.001, and HR: 2.05, p = 0.044, respectively) and overall survival (HR: 2.48, p = 0.026, and HR: 2.63, p = 0.008, respectively). - Conclusion: Our analysis represents one of the largest cohorts of EM AML and establishes key molecular markers linked to EM, providing new evidence that EM is associated with adverse risk in AML and may warrant allogeneic HCT in eligible patients with EM.