Issue Archive

Three articles in this week’s issue report phase 2 studies of daratumumab for the treatment of relapsed/refractory AL amyloidosis. Although their results vary widely, reflecting differences in inclusion criteria, study size, and duration of therapy, all three confirm that daratumumab is a highly effective agent for the treatment of this advanced disease in some patients.

Three articles in this week’s issue report phase 2 studies of daratumumab for the treatment of relapsed/refractory AL amyloidosis. Although their results vary widely, reflecting differences in inclusion criteria, study size, and duration of therapy, all three confirm that daratumumab is a highly effective agent for the treatment of this advanced disease in some patients.

Three articles in this week’s issue report phase 2 studies of daratumumab for the treatment of relapsed/refractory AL amyloidosis. Although their results vary widely, reflecting differences in inclusion criteria, study size, and duration of therapy, all three confirm that daratumumab is a highly effective agent for the treatment of this advanced disease in some patients.

Boettcher and colleagues analyzed clonal hematopoiesis (CH) in 42 donor-recipient pairs of long-term survivors of allogeneic stem cell transplantation. CH is prevalent among both donors and recipients, including a small number of recipients with engraftment of donor CH; these clones variably expand between donor and recipient.

CDK6 is overexpressed in Philadelphia chromosome–positive acute lymphocytic leukemia (Ph⁺ ALL) and is required for leukemia cell growth and survival. De Dominici et al demonstrated that a novel proteolysis-targeting chimera (PROTAC) that binds CDK6 and a proteasome-targeting E3 ubiquitin ligase has impressive activity against Ph-positive ALL cells in vitro and in vivo.

Nagy et al elucidate the role of Src family kinases (SFKs) and their regulating tyrosine kinases Chk, Csk, and PTPRJ in determination of platelet number. Through a series of knockout experiments, they demonstrated an intricate interplay among the three kinases and SFKs themselves in inhibiting megakaryocyte proliferation.

Jung and colleagues performed a thorough genotype-phenotype analysis of FANCB, the only X-linked variant of Fanconi anemia. FANCB patients are generally characterized by early-onset bone marrow failure and severe congenital abnormalities. However, variations in causative mutations lead to different functional properties that modulate clinical severity.

Truncation mutations in the granulocyte colony-stimulating factor receptor gene (CSF3R) are a rare abnormality in pediatric acute myeloid leukemia, and are usually associated either with mutations in CEBPA or with t(8;21). Through sequencing of over 2000 patients, the authors demonstrated that, although CSF3R mutations with associated t(8;21) still had an excellent response, CSF3R mutation abrogated the favorable risk of CEBPA mutation alone.