GATA2 zinc finger 2 mutation found in acute myeloid leukemia impairs myeloid differentiation

AbstractWe identified two novel GATA2 mutations in acute myeloid leukemia (AML). One mutation (p.R308P-GATA2) was a R308P substitution within the zinc finger (ZF)-1 domain, and the other (p.A350_N351ins8-GATA2) was an eight-amino-acid insertion between A350 and N351 residues within the ZF-2 domain. p.R308P-GATA2 did not affect DNA-binding and transcriptional activities, while p.A350_N351ins8-GATA2 reduced them, and impaired G-CSF-induced granulocytic differentiation of 32D cells. Although p.A350_N351ins8-GATA2 did not show a dominant-negative effect over wild-type (Wt)–GATA2 by the reporter assay, it might be involved in the pathophysiology of AML by impairing myeloid differentiation because of little Wt-GATA2 expression in primary AML cells harboring the p.A350_N351ins8 mutation

Diffuse large B cell lymphoma primarily presenting as acute liver failure in a surviving patient

Acute liver failure (ALF) is a relatively rare presentation of non-Hodgkin lymphoma, often found only during postmortem examination in patients. We treated a 33-year-old woman with prominent jaundice who was diagnosed with diffuse large B-cell lymphoma presenting as ALF. We could not perform liver biopsy during the critical phase because of coagulopathy, but gastric biopsy showed the infiltration of lymphoma cells. The patient was successfully treated with rituximab and chemotherapy and she survived. Malignant lymphoma should be considered in the differential diagnosis of patients who show liver dysfunction, and biopsy should be performed

PCSK5 mutation in a patient with the VACTERL association

Background: The VACTERL association is a typically sporadic, non-random collection of congenital anomalies that includes vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula with esophageal atresia, renal anomalies, and limb abnormalities. Although several chromosomal aberrations and gene muta tions have been reported as disease-causative, these findings have been sparsely replicated to date. Case presentation: In the present study, whole exome sequencing of a case with the VACTERL association uncovered a novel frameshift mutation in the PCSK5 gene, which has been reported as one of the causative genes for the VACTERL association. Although this mutation appears potentially pathogenic in its functional aspects, it was also carried by the healthy father. Furthermore, a database survey revealed several other deleterious variants in the PCSK5 gene in the general population. Conclusions: Further studies are necessary to clarify the etiological role of the PCSK5 mutation in the VACTERL association. Electronic supplementary material The online version of this article (doi:10.1186/s13104-015-1166-0) contains supplementary material, which is available to authorized users

Autologous peripheral blood stem cell transplantation for Philadelphia chromosome‐positive acute lymphoblastic leukemia is safe but poses challenges for long‐term maintenance of molecular remission: Results of the Auto‐Ph17 study

Abstract Autologous hematopoietic stem cell transplantation (SCT) is not a standard treatment option for Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph+ALL); however, its position has been reassessed since the introduction of tyrosine kinase inhibitors (TKIs). We prospectively analyzed the efficacy and safety of autologous peripheral blood SCT (auto‐PBSCT) for Ph+ALL patients aged between 55 and 70 years who had achieved complete molecular remission. Melphalan, cyclophosphamide, etoposide, and dexamethasone were used for conditioning. A total of 12 courses of maintenance therapy, including dasatinib, were performed. The required number of CD34+ cells was harvested in all five patients. No patient died within 100 days after auto‐PBSCT, and no unexpected serious adverse events were observed. Although 1‐year event‐free survival was 100%, hematological relapse was observed in three patients at a median of 801 days (range, 389–1088 days) after auto‐PBSCT. Molecular progressive disease was observed in the other two patients, although they maintained their first hematological remission at the last visit. Auto‐PBSCT can be safely performed for Ph+ALL with TKIs. A limitation of auto‐PBSCT was suggested, despite the increase in the intensity of a single treatment. The development of long‐term therapeutic strategies by including new molecular targeted drugs is warranted to maintain long‐term molecular remission