Diagnosis of systemic mastocytosis with cryptic deletion of TET2 and DNMT3A resulting from unbalanced translocation.

Systemic mastocytosis (SM) is a rare haematological neoplasm associated with the gain of function mutation KIT D816V in 90% of adult patients. Classically, cytogenetic aberrations are not common except in cases of SM associated with another haematological neoplasm. We highlight here an unusual clinical presentation of SM and demonstrate the utility of advanced cytogenetic analysis (optical genome mapping, OGM) in detecting a novel cytogenetic abnormality resulting in an unusual mechanism of DNMT3A and TET2 loss of function.

Breakthrough Invasive Fungal Infection After Coadministration of Venetoclax and Voriconazole.

Venetoclax requires a 75% dose reduction when coadministered with voriconazole. In a 10-year historical cohort of treatment with venetoclax, we did not observe a worse hematologic outcome in patients who received voriconazole prophylaxis versus those who did not. Subtherapeutic voriconazole levels and a triazole exposure history may contribute to breakthrough invasive fungal infection.

A Case of Clinical Confusion Due to Erroneous M-protein Quantifications: To Splice or Skim?

An M-protein identified on electrophoresis is conventionally quantified by integrating the M-spike from baseline (PD), invariably including some irrelevant/background proteins. The use of an alternative approach that skims the M-spike tangentially thereby excluding the background proteins (TS), however, has been scanty. We report herein a case in which PD overestimated the M-proteins inconsistently, leading to confusion over relapse in a multiple myeloma patient.

A link between hypercholesterolemia and chronic lymphocytic leukemia.

The incidence of hypercholesterolemia and its possible relationship with clinical course were determined by reviewing the records of 231 consecutive patients presenting to a specialized Chronic Lymphocytic Leukemia (CLL) clinic. Evidence for elevated cholesterol was found in up to 174/231 patients (75%) based on existing use of statins (107 patients) or non-fasting low-density lipoprotein cholesterol levels greater than 2.5 mM.

Predictors of unsuccessful mobilization with granulocyte colony-stimulating factor alone in patients undergoing autologous hematopoietic stem cell transplantation.

Mobilization of hematopoietic stem cells is achieved with hematopoietic growth factors with or without chemotherapy or other agents. Although studies comparing granulocyte colony-stimulating factor (G-CSF) alone to combined regimens demonstrate an increase in stem cell yield in the latter, mobilization with G-CSF alone is still effective and has been widely practiced. We conducted a retrospective cohort study of consecutive patients at our institution who underwent at least one mobilization attempt with G-CSF between January 2000 and December 2008 to identify the proportion of patients failing one or more mobilization attempts and the potential predictors of mobilization failure with this regime.

Proline residues in transmembrane segment IV are critical for activity, expression and targeting of the Na+/H+ exchanger isoform 1.

NHE1 (Na+/H+ exchanger isoform 1) is a ubiquitously expressed integral membrane protein that regulates intracellular pH in mammalian cells. Proline residues within transmembrane segments have unusual properties, acting as helix breakers and increasing flexibility of membrane segments, since they lack an amide hydrogen. We examined the importance of three conserved proline residues in TM IV (transmembrane segment IV) of NHE1.