Distinct bone marrow immunophenotypic features define the splicing factor 3B subunit 1 (SF3B1)-mutant myelodysplastic syndromes subtype.

Splicing factor 3B subunit 1 (SF3B1) mutations define a distinct myelodysplastic syndromes (MDS) patient group with a relatively favourable disease course and high response rates to luspatercept. Few data are available on bone marrow phenotype beyond ring sideroblasts in this subgroup of patients with MDS. In the present study, we identified immunophenotypic erythroid, myelomonocyte and progenitor features associated with SF3B1 mutations. In addition, we illustrate that SF3B1-mutation type is associated with distinct immunophenotypic features, and show the impact of co-occurrence of a SF3B1 mutation and a deletion of chromosome 5q on bone marrow immunophenotype. These genotype-phenotype associations and phenotypic subtypes within SF3B1-MDS provide leads that may further refine prognostication and therapeutic strategies for this particular MDS subgroup.

Prognostic importance of the extent of ulceration in patients with clinically localized cutaneous melanoma.

OBJECTIVE: To determine the prognostic value of the extent of ulceration, categorized as diameter of ulceration and as percentage of invasive melanoma diameter. BACKGROUND: Ulceration is an adverse prognostic factor for clinically localized primary cutaneous melanoma. However, the prognostic significance of the extent of ulceration remains unclear. METHODS: Clinicopathologic and follow-up data on 4661 patients treated at a single center were analyzed. RESULTS: Both the presence and extent of ulceration were independent predictors of survival. The 5-year melanoma-specific survival (MSS) for ulcerated and nonulcerated melanomas was 77.6% and 91.3%, respectively. The 5-year MSS for minimally/moderately ulcerated melanomas (≤70% or ≤5 mm) was 80.4% and 82.7%, respectively, compared to extensively ulcerated melanomas (>70% or >5 mm), which had a 5-year MSS of 66.4% and 59.3%. On multivariate analysis, tumor thickness and the presence/absence of mitoses were the most powerful predictors of MSS. The presence of ulceration was also an independent predictor of poorer MSS (hazard ratio [HR] = 1.55, P < 0.001). Patients with minimally/moderately ulcerated tumors (≤70% or ≤5 mm) had a significantly higher risk of death (HR = 1.53 and HR = 1.39, respectively) compared to nonulcerated melanoma, as did patients with extensively ulcerated tumors (>70%: HR = 2.20 and >5 mm: HR = 2.03). CONCLUSIONS: Extent of ulceration (measured either as diameter or percentage of tumor width) provides more accurate prognostic information than the mere presence of ulceration. This has potential implications for melanoma patients with regard to prognosis, staging, management, and eligibility for clinical trials. We recommend that extent of ulceration be recorded in pathology reports for all ulcerated primary cutaneous melanomas.

[Medicinal cannabis]. / Medicinale cannabis.

Medicinal cannabis The use of cannabis products for medical purposes is rapidly increasing in the Netherlands. Studies suggest that these products have positive effects in the treatment of chronic neuropathic pain, multiple-sclerosis-related spasticity, certain epilepsy syndromes and chemotherapy-related nausea and vomiting. The interpretation of these findings is impeded by methodological shortcomings, such as a small number of participants. Differences in product composition and dosage form mean that study resultsare often not directly comparable. Responsible prescribing requires that the patient be very well informed about the goal of treatment, alternative forms of treatment and the side effects. A history of psychosis, relevant cardiac co-morbidity, recurrent falls, addiction problems, pregnancy and breastfeeding are all contra-indications to the use of medical cannabis.

TCF4 promotes erythroid development.

Transcription factor 4 (TCF4) is implicated in lymphoid cell differentiation and its expression predicts outcome in acute myeloid leukemia. Here, we investigated the role of TCF4 in myelopoiesis. Overexpression of TCF4 (TCF4OE) in umbilical cord blood (UCB) cells resulted in a twofold increase in erythroid colony forming units (CFU-Es), whereas knock-down (KD) of TCF4 (TCF4KD) caused a dramatic decrease in the number of erythroid colonies. In megakaryocyte CFUs (CFU-MKs), both TCF4KD and TCF4OE inhibited MK colony formation. TCF4 did not have an impact on granulocyte, macrophage, or granulocyte-macrophage colonies or on the proportion of MK-erythrocyte progenitors (MEPs) in culture. Because TCF4 affects erythroid/MK development and these lineages are affected in myelodysplastic syndrome (MDS), we studied the impact of TCF4 expression in this disease. MDS patients with high (≥median) TCF4 mRNA expression had higher hemoglobin (Hb) levels than MDS patients with low TCF4 expression (mean 9.0 vs. 8.55 g/dL, p = 0.02). Overall, TCF4 mRNA expression was lower in hematopoietic stem cells, common myeloid progenitors, and MEPs from MDS patients, but not in granulocyte-macrophage progenitors, compared with healthy controls. Therefore, in cell fractions with erythroid lineage potential, TCF4 is expressed less in MDS patients than in healthy controls. This correlates with the low overall Hb levels seen in MDS patients compared with healthy individuals and is consistent with the positive impact of TCF4 on erythroid development while not having impact on white colonies. These results indicate a role for TCF4 as a novel factor in erythroid-megakaryocytic differentiation.