Clinical and imaging characteristics of patients with cardiac amyloidosis- a single center observational study.

Amyloidosis is a disease characterized by the deposition of protein fibrils. Cardiac involvement is a significant factor in determining prognosis. This study aimed to examine the clinical profile, outcomes, and long-term mortality rates in patients with transthyretin (ATTR) and amyloid light-chain (AL) amyloidosis. The retrospective cohort study included 94 patients with amyloidosis (69 with AL and 25 with ATTR amyloidosis) diagnosed between 2010 and 2022. The study involved multimodality imaging (ECG, echocardiography and cardiac magnetic resonance (CMR) data and survival analyses. Patients with ATTR amyloidosis were older and had a higher proportion of males compared to those with AL amyloidosis. Cardiac involvement was more prevalent in the ATTR group, including atrial fibrillation (AF), while pleural and pericardial effusion were more frequent in the AL group. Biomarkers such as NT-proBNP and troponin T were significantly elevated in both groups and were associated with all-cause mortality only in univariate analyses. CMR data, especially typical late gadolinium enhancement (LGE) was not associated with increased mortality, while pleural effusion and left atrial dilatation on echocardiography were identified as powerful predictors of mortality. In conclusion, both AL and ATTR amyloidosis exhibited poor outcomes. Cardiac involvement, particularly dilated left atrium and pleural effusion on echocardiography were associated with an increased risk of mortality, while typical LGE on CMR was not.

Monocytic Differentiation in Acute Myeloid Leukemia Cells: Diagnostic Criteria, Biological Heterogeneity, Mitochondrial Metabolism, Resistance to and Induction by Targeted Therapies.

We review the importance of monocytic differentiation and differentiation induction in non-APL (acute promyelocytic leukemia) variants of acute myeloid leukemia (AML), a malignancy characterized by proliferation of immature myeloid cells. Even though the cellular differentiation block is a fundamental characteristic, the AML cells can show limited signs of differentiation. According to the French-American-British (FAB-M4/M5 subset) and the World Health Organization (WHO) 2016 classifications, monocytic differentiation is characterized by morphological signs and the expression of specific molecular markers involved in cellular communication and adhesion. Furthermore, monocytic FAB-M4/M5 patients are heterogeneous with regards to cytogenetic and molecular genetic abnormalities, and monocytic differentiation does not have any major prognostic impact for these patients when receiving conventional intensive cytotoxic therapy. In contrast, FAB-M4/M5 patients have decreased susceptibility to the Bcl-2 inhibitor venetoclax, and this seems to be due to common molecular characteristics involving mitochondrial regulation of the cellular metabolism and survival, including decreased dependency on Bcl-2 compared to other AML patients. Thus, the susceptibility to Bcl-2 inhibition does not only depend on general resistance/susceptibility mechanisms known from conventional AML therapy but also specific mechanisms involving the molecular target itself or the molecular context of the target. AML cell differentiation status is also associated with susceptibility to other targeted therapies (e.g., CDK2/4/6 and bromodomain inhibition), and differentiation induction seems to be a part of the antileukemic effect for several targeted anti-AML therapies. Differentiation-associated molecular mechanisms may thus become important in the future implementation of targeted therapies in human AML.

Monocytic Differentiation of Human Acute Myeloid Leukemia Cells: A Proteomic and Phosphoproteomic Comparison of FAB-M4/M5 Patients with and without Nucleophosmin 1 Mutations.

Even though morphological signs of differentiation have a minimal impact on survival after intensive cytotoxic therapy for acute myeloid leukemia (AML), monocytic AML cell differentiation (i.e., classified as French/American/British (FAB) subtypes M4/M5) is associated with a different responsiveness both to Bcl-2 inhibition (decreased responsiveness) and possibly also bromodomain inhibition (increased responsiveness). FAB-M4/M5 patients are heterogeneous with regard to genetic abnormalities, even though monocytic differentiation is common for patients with Nucleophosmin 1 (NPM1) insertions/mutations; to further study the heterogeneity of FAB-M4/M5 patients we did a proteomic and phosphoproteomic comparison of FAB-M4/M5 patients with (n = 13) and without (n = 12) NPM1 mutations. The proteomic profile of NPM1-mutated FAB-M4/M5 patients was characterized by increased levels of proteins involved in the regulation of endocytosis/vesicle trafficking/organellar communication. In contrast, AML cells without NPM1 mutations were characterized by increased levels of several proteins involved in the regulation of cytoplasmic translation, including a large number of ribosomal proteins. The phosphoproteomic differences between the two groups were less extensive but reflected similar differences. To conclude, even though FAB classification/monocytic differentiation are associated with differences in responsiveness to new targeted therapies (e.g., Bcl-2 inhibition), our results shows that FAB-M4/M5 patients are heterogeneous with regard to important biological characteristics of the leukemic cells.

A woman in her thirties with dyspnoea two weeks after abdominoplasty. / En kvinne i 30-årene med dyspné to uker etter bukplastikkoperasjon.

Background: While most cases of venous thromboembolism follow a benign course, occasionally the condition may manifest a complex clinical presentation and need a comprehensive diagnostic workup to identify the underlying cause and provide the patient with appropriate treatment. Case presentation: A woman in her late thirties presented to the emergency department with a five-day history of dyspnoea. She had recently undergone liposuction surgery after pregnancy. Upon admission, initial investigations revealed a pulmonary embolism with right heart strain, and she was treated with anticoagulants. The following day, she complained of acute-onset right flank pain without fever or other accompanying symptoms. A CT scan of the abdomen confirmed a right-side renal infarction. Further investigations revealed patent foramen ovale between the right and left atria of the heart, believed to be the source of a right-to-left shunt of arterial emboli. Although the patient had not suffered a clinical stroke, it was decided to close this defect using percutaneous technique. Interpretation: Patent foramen ovale is a common condition in adults, but in most cases it remains asymptomatic. However, patients with patent foramen ovale have an elevated risk of arterial emboli affecting multiple organs. The diagnosis depends on thorough assessment to prevent potentially fatal outcomes.

Safety of hypoxic red blood cell administration in patients with transfusion-dependent hematological malignancies: An interim analysis.

Anemia is a common symptom of hematological malignancies and red blood cell (RBC) transfusion is the primary supportive treatment, with many patients becoming transfusion dependent. Hemanext Inc. (Lexington, MA, United States) has developed a CE mark certified device to process and store RBCs hypoxically - citrate-phosphatedextrose (CPD)/phosphate-adenine-glucose-guanosine-saline-mannitol (PAGGSM) RBCs, leukocytes-reduced (LR), O2/CO2 reduced - with the aim of improving RBC quality for transfusion. This interim analysis describes the first patients to receive hypoxic RBCs, administered as part of a pilot post-marketing study in Norway. The primary outcome was adverse events (AEs) within 24 h of transfusion initiation and overall up to 7 days ( ± 1 day) post-transfusion. Secondary outcomes included changes in hemoglobin levels post-transfusion. Five patients with hematological malignancies were included (80 % male, mean age 69.8 [SD ± 19.3] years). Prior to the study, patients had been receiving conventional RBC transfusions every two weeks. Patients received 2 units of hypoxic RBCs over 2 h without complication. One mild AE (rhinovirus) was reported two days post-treatment and was deemed unrelated to treatment. The mean ± SD pre-transfusion hemoglobin level was 7.7 ± 0.5 g/dL, evolving to 9.0 ± 0.9 g/dL following administration of hypoxic RBCs; an increase of 17 %. This interim analysis showed that transfusion with hypoxic RBCs processed with the CPD/PAGGSM LR, O2/CO2 reduced system was effective and well tolerated in patients with hematologic malignancies. The overall clinical program will assess whether the use of hypoxic RBCs can reduce transfusion interval versus conventional RBCs in patients requiring acute and chronic transfusions.

Frequency of JAK2V617F, MPL and CALR driver mutations and associated clinical characteristics in a Norwegian patient cohort with myeloproliferative neoplasms.

Myeloproliferative neoplasms are hematological disorders characterized by increased production in one or more myeloid cell lines, associated with driver mutations in JAK2-, MPL- and CALR-genes. The aims of this study were to investigate the prevalence of these driver mutations in a Norwegian patient cohort with myeloproliferative neoplasms, and to assess whether the different mutations were associated with different clinical presentation and natural history.Results from 820 patients in whom analysis for JAK2V617F-, CALR- and MPL had been performed at Haukeland University Hospital in the period 2014-2019 were retrieved and analyzed together with clinical variables related to diagnosis, hematological blood parameters and complications, obtained from patient records.We identified 182 cases of myeloproliferative neoplasms: 78 with JAK2V617F, 28 with CALR-mutations, two with MPL-mutations and 23 cases without a driver mutation. There was a lower prevalence of JAK2V617F mutation than expected in the polycythemia vera group, likely related to overdiagnosis. In patients with essential thrombocytosis, we found significantly higher levels of hemoglobin and erythrocyte volume fraction for JAK2V617F-mutated disease, and significantly higher levels of platelets and lactate dehydrogenase for CALR-mutated disease. Patients with JAK2V617F-mutated primary myelofibrosis had significantly higher levels of hemoglobin, and there was an increased number of smokers or former smokers in this group compared to patients with CALR-mutations.Except for a lower prevalence of JAK2V617F-mutation in polycythemia vera, the mutational distribution in our patient cohort was similar to previous findings in other populations. The novel finding of a higher prevalence of smokers in JAK2V617F-mutated primary myelofibrosis warrants further investigation.

En mann i 40-årene med transfusjonskrevende anemi.

BACKGROUND: While standard blood tests are often sufficient for an anaemia workup, sometimes more invasive diagnostic testing is required to exclude rare conditions. CASE PRESENTATION: A man in his forties contacted his general practitioner because of increasing functional dyspnoea. He had completed a course of dicloxacillin a few months previously for a skin abscess on his abdomen. Bloodwork revealed severe anaemia (haemoglobin 5.4 g/dL), which required transfusion. Subsequent testing excluded iron and vitamin deficiency anaemia, haemolysis and malignancy. Initial bone marrow biopsy was of suboptimal quality. However, repeat tissue sample supported a diagnosis of pure red cell aplasia. The patient improved with ciclosporin treatment, which was gradually tapered. INTERPRETATION: Pure red cell aplasia should be considered in patients with new onset isolated anaemia with severe reticulocytopenia. Diagnosis depends on obtaining representative tissue from bone marrow biopsy. It is difficult to conclude for this patient whether the aetiology of his pure red cell aplasia was idiopathic or secondary to recent dicloxacillin use.

Weight gain during treatment course of allogenic hematopoietic stem cell transplantation in patients with hematological malignancies affects treatment outcome.

BACKGROUND AIMS: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for patients with hematological malignancies; however, allo-HSCT does not come without the cost of treatment-related morbidity and mortality. Early detection of risk factors could be helpful in identifying patients who could benefit from early interventions. Many patients gain weight during the allo-HSCT treatment, although little is known about the impact of weight gain. METHODS: Weight gain in 146 consecutively enrolled adult patients undergoing allo-HSCT was explored. RESULTS: In total, 141 patients (97%) gained weight along the course of allo-HSCT. Median weight increase was 4.8 kg (range 0.0-16.1 kg), with median increase in body weight 6.5% (range 0.0%-30.8%). Maximum weight increase was observed at day +7 (range day -8, +44). Weight gain was associated with increased incidence of acute graft-versus-host disease. Patients with weight gain >10% had a significantly greater 5-year mortality compared with those with lower weight gain (P = 0.031, rank sum test). CONCLUSIONS: Weight gain is a simple variable with the ability to provide prognostic information for patients undergoing allo-HSCT.

Heterogeneity of Patient-Derived Acute Myeloid Leukemia Cells Subjected to SYK In Vitro Inhibition.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a dismal prognosis. The cytoplasmic spleen tyrosine kinase (SYK) is highly expressed by hematopoietic cells and has emerged as a potential therapeutic target. In this study, we evaluated the in vitro antileukemic effects of five SYK inhibitors, fostamatinib, entospletinib, cerdulatinib, TAK-659, and RO9021, in a consecutive AML patient cohort. All inhibitors demonstrated a concentration-dependent antiproliferative effect, although there was considerable heterogeneity among patients. For fostamatinib and TAK-659, the antiproliferative effects were significantly higher in FLT3 mutated patients compared to nonmutated patients. Fostamatinib, entospletinib, TAK-659, and RO9021 induced significant apoptosis in primary AML cells, although the proapoptotic effects of the SYK inhibitors were less pronounced than the antiproliferative effects. Finally, most of the SYK inhibitors caused a significant decrease in the release of cytokines and chemokines from primary AML cells, indicating a potent inhibitory effect on the release of these leukemic signaling molecules. We concluded that the SYK inhibitors had antileukemic effects in AML, although larger studies are strongly needed to identify which patient subsets will benefit most from such a treatment.

Toll-like Receptor 4, Osteoblasts and Leukemogenesis; the Lesson from Acute Myeloid Leukemia.

Toll-like receptor 4 (TLR4) is a pattern-recognizing receptor that can bind exogenous and endogenous ligands. It is expressed by acute myeloid leukemia (AML) cells, several bone marrow stromal cells, and nonleukemic cells involved in inflammation. TLR4 can bind a wide range of endogenous ligands that are present in the bone marrow microenvironment. Furthermore, the TLR4-expressing nonleukemic bone marrow cells include various mesenchymal cells, endothelial cells, differentiated myeloid cells, and inflammatory/immunocompetent cells. Osteoblasts are important stem cell supporting cells localized to the stem cell niches, and they support the proliferation and survival of primary AML cells. These supporting effects are mediated by the bidirectional crosstalk between AML cells and supportive osteoblasts through the local cytokine network. Finally, TLR4 is also important for the defense against complicating infections in neutropenic patients, and it seems to be involved in the regulation of inflammatory and immunological reactions in patients treated with allogeneic stem cell transplantation. Thus, TLR4 has direct effects on primary AML cells, and it has indirect effects on the leukemic cells through modulation of their supporting neighboring bone marrow stromal cells (i.e., modulation of stem cell niches, regulation of angiogenesis). Furthermore, in allotransplant recipients TLR4 can modulate inflammatory and potentially antileukemic immune reactivity. The use of TLR4 targeting as an antileukemic treatment will therefore depend both on the biology of the AML cells, the biological context of the AML cells, aging effects reflected both in the AML and the stromal cells and the additional antileukemic treatment combined with HSP90 inhibition.

Types of exams used in medical education in Norway. / Eksamensformer i de norske medisinstudiene.

BACKGROUND: No overview exists of the types of exams used in medical education in Norway. In this study, we have identified these and analysed the reasons why directors of studies choose a particular type of exam. The aim has been to form an overview and to frame the reasoning behind assessment practices in Norwegian undergraduate medical education in an international and research-based perspective. MATERIAL AND METHOD: We gathered information about the types of exams used in the four undergraduate medical education programmes in Norway. We also conducted semi-structured interviews with a director of studies at each university. The strengths and weaknesses of the types of exams used were discussed in the interviews. RESULTS: The number of exams, the types of exams and their position in the study programme varied considerably across the four study programmes. Multiple-choice exams were the most common, supplemented with various oral exams and practical assessments. Arguments for choosing the various types of exam were largely related to the need for standardisation, objectivity and resource availability. INTERPRETATION: Assessment seems to be largely intended to measure and control, while the opportunities to foster learning that examination affords are not well exploited. Systems thinking in relation to the different intentions of the types of assessment, which is touched on in international guidelines, seems to be a low priority.

A young woman with dyspnoea and proteinuria. / En ung kvinne med pustevansker og proteinuri.

BACKGROUND: Systemic lupus erythematosus and anti-phospholipid syndrome may cause severe haematological complications despite few other symptoms of disease. CASE PRESENTATION: A previously healthy woman in her late twenties was admitted to hospital with chest pain and dyspnoea. CT of the thorax revealed bilateral pulmonary embolism and urine sampling showed haematuria and proteinuria. A few days after hospital admission, she developed transfusion-requiring anaemia. The investigation revealed a positive direct antiglobulin test, presence of anti-nuclear antibodies, lupus anticoagulant, anti-cardiolipin and anti-glycoprotein antibodies. INTERPRETATION: Pulmonary embolism in a young, previously healthy woman may be caused by different predisposing conditions. Systemic lupus erythematosus with accompanying anti-phospholipid syndrome was the diagnosis in this case. Severe autoimmune haemolytic disease may occur as a secondary phenomenon to systemic lupus erythematosus, and the condition must not be overlooked.

The PI3K-Akt-mTOR Signaling Pathway in Human Acute Myeloid Leukemia (AML) Cells.

Acute myeloid leukemia (AML) is a heterogeneous group of diseases characterized by uncontrolled proliferation of hematopoietic stem cells in the bone marrow. Malignant cell growth is characterized by disruption of normal intracellular signaling, caused by mutations or aberrant external signaling. The phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway (PI3K-Akt-mTOR pathway) is among one of the intracellular pathways aberrantly upregulated in cancers including AML. Activation of this pathway seems important in leukemogenesis, and given the central role of this pathway in metabolism, the bioenergetics of AML cells may depend on downstream signaling within this pathway. Furthermore, observations suggest that constitutive activation of the PI3K-Akt-mTOR pathway differs between patients, and that increased activity within this pathway is an adverse prognostic parameter in AML. Pharmacological targeting of the PI3K-Akt-mTOR pathway with specific inhibitors results in suppression of leukemic cell growth. However, AML patients seem to differ regarding their susceptibility to various small-molecule inhibitors, reflecting biological heterogeneity in the intracellular signaling status. These findings should be further investigated in both preclinical and clinical settings, along with the potential use of this pathway as a prognostic biomarker, both in patients receiving intensive curative AML treatment and in elderly/unfit receiving AML-stabilizing treatment.

Hyperferritinaemia-cataract syndrome. / Hyperferritinemi-katarakt-syndrom.

BACKGROUND: Elevated serum ferritin levels are common findings in clinical practice, usually caused by inflammation, liver disease, high alcohol consumption or malignancy, although it can occur in association with rare genetic conditions. CASE PRESENTATION: We describe a male in his sixties with persistent hyperferritinaemia without associated iron overload and subsequent development of cataract. The patient himself suggested hyperferritinaemia-cataract syndrome as a diagnosis, which was subsequently confirmed with mutation analysis of the light chain ferritin (FTL) gene. Such mutations are inherited in an autosomal dominant pattern. INTERPRETATION: Mutations in FTL are known to interfere with the balance between iron levels and ferritin production. When common causes of hyperferritinaemia are excluded, rare conditions should be considered in order to avoid unnecessary procedures and treatment. Genetic analyses are available for all clinicians and should be requested upon the right indications.

Treatment of acute myeloid leukaemia in elderly patients. / Behandling av akutt myelogen leukemi hos eldre.

Acute myeloid leukaemia is a group of aggressive, malignant haematological diseases that affect all age groups, but are most common in older persons over 65 years of age. Recent therapeutic methods and research indicate that older patients may also benefit from more active treatment.

The healthy donor profile of immunoregulatory soluble mediators is altered by stem cell mobilization and apheresis.

BACKGROUND: Peripheral blood stem cells from healthy donors mobilized by granulocyte colony-stimulating factor (G-CSF) and thereafter harvested by leukapheresis are commonly used for allogeneic stem cell transplantation. METHODS: Plasma levels of 38 soluble mediators (cytokines, soluble adhesion molecules, proteases, protease inhibitors) were analyzed in samples derived from healthy stem cell donors before G-CSF treatment and after 4 days, both immediately before and after leukapheresis. RESULTS: Donors could be classified into two main subsets based on their plasma mediator profile before G-CSF treatment. Seventeen of 36 detectable mediators were significantly altered by G-CSF; generally an increase in mediator levels was seen, including pro-inflammatory cytokines, soluble adhesion molecules and proteases. Several leukocyte- and platelet-released mediators were increased during apheresis. Both plasma and graft mediator profiles were thus altered and showed correlations to graft concentrations of leukocytes and platelets; these concentrations were influenced by the apheresis device used. Finally, the mediator profile of the allotransplant recipients was altered by graft infusion, and based on their day +1 post-transplantation plasma profile our recipients could be divided into two major subsets that differed in overall survival. DISCUSSION: G-CSF alters the short-term plasma mediator profile of healthy stem cell donors. These effects together with the leukocyte and platelet levels in the graft determine the mediator profile of the stem cell grafts. Graft infusion also alters the systemic mediator profile of the recipients, but further studies are required to clarify whether such graft-induced alterations have a prognostic impact.

Cytokine profiling and post-transfusion haemoglobin increment in patients with haematological diseases.

BACKGROUND AND OBJECTIVES: In a previous pilot study, we demonstrated significantly lower haemoglobin (Hb) increment after red-blood-cell (RBC) transfusions in febrile patients compared to patients without fever. The aim of this study was to examine associations between inflammatory mediators and post-transfusion haemoglobin increment in patients with haematological diseases. MATERIALS AND METHODS: Twenty-seven patients (eight women, 19 men), median age 56 years receiving RBC transfusion, were included in the study. Hb increment per unit transfused was corrected for estimated patient blood volume and the amount of Hb transfused. A wide spectrum of inflammatory mediators was determined by multiplex technology. Association between post-transfusion haemoglobin increment, plasma inflammatory mediators and patient characteristics was analysed using a mixed linear regression model. RESULTS: Febrile patients had significantly lower corrected Hb increment, significantly increased values of IL-6, IL-8, IL-10 and G-CSF, significantly reduced levels of CCL5 and CXCL10, and significantly higher pretransfusion levels of CRP. There was a significant association between pretransfusion CRP levels and corrected Hb increment for the whole patient cohort, but not within each of the two groups. Results demonstrated an association between haemoglobin increment, fever and inflammatory mediators. Febrile patients had a significantly lower corrected Hb increment compared to nonfebrile patients, when adjusting for mediators. When fever was kept constant, a significant negative association between haemoglobin increment and the proinflammatory mediators IL-6 and IL-8 was observed. CONCLUSION: Both fever and the inflammatory mediators IL-6 and IL-8 were negatively associated with post-transfusion haemoglobin increment.

Resistance to the Antiproliferative In Vitro Effect of PI3K-Akt-mTOR Inhibition in Primary Human Acute Myeloid Leukemia Cells Is Associated with Altered Cell Metabolism.

Constitutive signaling through the phosphatidylinositol-3-kinase-Akt-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway is present in acute myeloid leukemia (AML) cells. However, AML is a heterogeneous disease, and we therefore investigated possible associations between cellular metabolism and sensitivity to PI3K-Akt-mTOR pathway inhibitors. We performed non-targeted metabolite profiling to compare the metabolome differences of primary human AML cells derived from patients susceptible or resistant to the in vitro antiproliferative effects of mTOR and PI3K inhibitors. In addition, the phosphorylation status of 18 proteins involved in PI3K-Akt-mTOR signaling and the effect of the cyclooxygenase inhibitor indomethacin on their phosphorylation status was investigated by flow cytometry. Strong antiproliferative effects by inhibitors were observed only for a subset of patients. We compared the metabolite profiles for responders and non-responders towards PI3K-mTOR inhibitors, and 627 metabolites could be detected. Of these metabolites, 128 were annotated and 15 of the annotated metabolites differed significantly between responders and non-responders, including metabolites involved in energy, amino acid, and lipid metabolism. To conclude, leukemia cells that are susceptible or resistant to PI3K-Akt-mTOR inhibitors differ in energy, amino acid, and arachidonic acid metabolism, and modulation of arachidonic acid metabolism alters the activation of mTOR and its downstream mediators.

The Possible Importance of ß3 Integrins for Leukemogenesis and Chemoresistance in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is an aggressive bone marrow malignancy where the immature leukemia cells communicate with neighboring cells through constitutive cytokine release and through their cell surface adhesion molecules. The primary AML cells express various integrins. These heterodimeric molecules containing an α and a ß chain are cell surface molecules that bind extracellular matrix molecules, cell surface molecules and soluble mediators. The ß3 integrin (ITGB3) chain can form heterodimers only with the two α chains αIIb and αV. These integrins are among the most promiscuous and bind to a large number of ligands, including extracellular matrix molecules, cell surface molecules and soluble mediators. Recent studies suggest that the two ß3 integrins are important for leukemogenesis and chemosensitivity in human AML. Firstly, αIIb and ß3 are both important for adhesion of AML cells to vitronectin and fibronectin. Secondly, ß3 is important for the development of murine AML and also for the homing and maintenance of the proliferation for xenografted primary human AML cells, and for maintaining a stem cell transcriptional program. These last effects seem to be mediated through Syk kinase. The ß3 expression seems to be regulated by HomeboxA9 (HoxA9) and HoxA10, and the increased ß3 expression then activates spleen tyrosine kinase (Syk) and thereby contributes to cytokine hypersensitivity and activation of ß2 integrins. Finally, high integrin αV/ß3 expression is associated with an adverse prognosis in AML and decreased sensitivity to the kinase inhibitor sorafenib; this integrin can also be essential for osteopontin-induced sorafenib resistance in AML. In the present article, we review the experimental and clinical evidence for a role of ß3 integrins for leukemogenesis and chemosensitivity in AML.