Evaluating a CLL susceptibility variant in ITGB2 in families with multiple subtypes of hematological malignancies

Blackburn, Nicholas B.; Marthick, James R.; Banks, Annette; Charlesworth, Jac; Marsden, Kate; Lowenthal, Ray M.; Blangero, John; Dickinson, Joanne L.

doi:10.1182/blood-2017-03-774232

Cited by 8 publications

(8 citation statements)

References 10 publications

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“…These patients, who previously required prophylactic intravenous injections of bypassing agents, can now be better treated with a subcutaneous injection of emicizumab every 1 or 2 weeks. It is also effective in congenital hemophilia without inhibitors, with as little as one subcutaneous injection every 4 weeks [ 54 ]. Some patients with AHA have been treated with emicizumab outside clinical studies with interesting responses [ 55 ].…”

Section: Clinical Managementmentioning

confidence: 99%

Prevention and Management of Bleeding Episodes in Patients with Acquired Hemophilia A

Knöbl

2018

Drugs

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Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies inhibiting the function of coagulation factor VIII. It is characterized by spontaneous bleeding in patients with no previous family or personal history of bleeding. Although several large registries have collected clinical data on AHA, limited information is available on the optimal management of AHA because controlled clinical trials are lacking. AHA can easily be diagnosed if the problem (prolonged activated partial thromboplastin time in a bleeding patient) is recognized. After the effects of anticoagulants are excluded, low factor VIII activity and the detection of circulating inhibitors confirms the diagnosis. However, lack of familiarity with this rare condition may delay diagnosis and adequate therapy. Treatment of AHA is based on measures for prompt hemostatic control to stop (and prevent) bleeding, immunosuppression to eradicate the autoantibodies, and supportive care for the adverse effects of that treatment and patients’ often complex comorbidities. This article gives a comprehensive overview of the current knowledge about the pathophysiology, diagnosis, and treatment of AHA.

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Section: Clinical Managementmentioning

confidence: 99%

Prevention and Management of Bleeding Episodes in Patients with Acquired Hemophilia A

Knöbl

2018

Drugs

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“…None of the six previously proposed CLL risk genes from direct-to-sequencing or CNV analyses in family-based designs are located on the sex chromosomes. These are ITGB2 [10] , POT1, TERF2IP, ACD [11] , DLEU7 and IRF4 [13] . All remain to be replicated.…”

Section: Discussionmentioning

confidence: 99%

“…All remain to be replicated. Attempts to replicate recurrence of ITGB2 rs2230531 in families [ 12 ] or association in sporadic case-control designs have not been successful [ 53 ] . We did not find significant or suggestive evidence of segregation of any of these loci in our pedigree, although we are limited by investigating only one family.…”

Section: Discussionmentioning

confidence: 99%

“…Two family-based whole exome sequencing (WES) studies have been performed [10,11] . Rigorous statistical thresholds that account for the multiple phases and family-based expectations have not yet been defined for direct-to-sequencing family studies, hence these studies remain largely observational in nature.…”

Section: Introductionmentioning

confidence: 99%

“…They identified 6 families recurrent for an allele in ITGB2 [rs2230531 at 21q22.3, minor allele frequency (MAF) = 0.007]. However, recurrence of this variant was not replicated in a follow-up study of ITGB2 in 47 small families [ 12 ] . In a WES study of 66 families (no restriction made to sharing across multiple families), ITGB2 variants were not identified, but four different coding variants were found to be recurrent within 7 different small families, all in genes involving the shelterin complex (four in POT1 , one in ACD and two TERF2IP at 7q31.33, 16q22.1 and 16q23.1, respectively) [ 11 ] .…”

Section: Introductionmentioning

confidence: 99%

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