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Pathology Aug 2021We reviewed haematological investigations for 43 patients treated at a single centre with alectinib, an inhibitor of anaplastic lymphoma kinase (ALK) which is considered...
We reviewed haematological investigations for 43 patients treated at a single centre with alectinib, an inhibitor of anaplastic lymphoma kinase (ALK) which is considered standard first-line treatment for patients with ALK-rearranged advanced non-small cell lung cancer. Ninety-five percent of patients developed marked acanthocytosis, echinocytosis and/or spheroacanthocytosis, not observable with prior treatment with other ALK-inhibitors. Anaemia developed in 73% of patients (38% <100 g/L, 8% <80 g/L), though definite new haemolysis was present in only 11%. Eosin-5-maleimide binding was reduced in all assessed patients, and increased membrane cholesterol was identified in one patient assessed with lattice light sheet microscopy. We have identified a previously undescribed phenomenon whereby alectinib induces red cell membrane abnormalities in nearly all patients through an unclear, but likely ALK-independent, mechanism, resulting in mild anaemia without universal haemolysis.
Topics: Abetalipoproteinemia; Anaplastic Lymphoma Kinase; Anemia; Carbazoles; Carcinoma, Non-Small-Cell Lung; Hemolysis; Humans; Lung Neoplasms; Maleimides; Piperidines; Protein Kinase Inhibitors; Retrospective Studies
PubMed: 33618863
DOI: 10.1016/j.pathol.2020.10.023 -
Journal of Clinical Research in... Jun 2020
Topics: Abetalipoproteinemia; Genes; Humans; Hypothyroidism; Mutation; Thymine Nucleotides
PubMed: 32157853
DOI: 10.4274/jcrpe.galenos.2020.2020.0015 -
Journal of Clinical Lipidology 2021"Normotriglyceridemic abetalipoproteinemia (ABL)" was originally described as a clinical entity distinct from either ABL or hypobetalipoproteinemia. Subsequent studies...
"Normotriglyceridemic abetalipoproteinemia (ABL)" was originally described as a clinical entity distinct from either ABL or hypobetalipoproteinemia. Subsequent studies identified mutations in APOB gene which encoded truncated apoB longer than apoB48. Therefore, "Normotriglyceridemic ABL" can be a subtype of homozygous familial hypobetalipoproteinemia. Here, we report an atypical female case of ABL who was initially diagnosed with "normotriglyceridemic ABL", because she had normal plasma apoB48 despite the virtual absence of apoB100 and low plasma TG level. Next generation sequencing revealed that she was a compound heterozygote of two novel MTTP mutations: nonsense (p.Q272X) and missense (p.G709R). We speculate that p.G709R might confer residual triglyceride transfer activity of MTTP preferentially in the intestinal epithelium to the hepatocytes, allowing production of apoB48. Together, "normotriglyceridemic ABL" may be a heterogenous disorder which is caused by specific mutations in either APOB or MTTP gene.
Topics: Abetalipoproteinemia; Adult; Aged; Apolipoprotein B-100; Apolipoprotein B-48; Biomarkers; Carrier Proteins; Female; Heterozygote; Humans; Male; Mutation
PubMed: 34052173
DOI: 10.1016/j.jacl.2021.04.013 -
JPGN Reports Feb 2021Supplemental Digital Content is available in the text.
Supplemental Digital Content is available in the text.
PubMed: 37206948
DOI: 10.1097/PG9.0000000000000049