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Telomere Length and Clonal Chromosomal Alterations in Peripheral Blood Samples of Patients with Severe Aplastic Anemia

Strauss, Joshua (2023) Telomere Length and Clonal Chromosomal Alterations in Peripheral Blood Samples of Patients with Severe Aplastic Anemia. Master Essay, University of Pittsburgh.

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Severe aplastic anemia (SAA) is a rare life-threatening bone marrow failure disorder. The standard of care for those patients involves allogeneic hematopoietic stem cell transplantation (HCT) as a first line of therapy for young patients with available matched sibling donor or immunosuppression with/or without HCT for older patients or those who need alternative donors. Both short telomeres and the presence of certain cytogenetic abnormalities have been associated with disease prognosis.
This study aimed to investigate the association between telomere length (TL) and mosaic chromosomal alterations (mCAs) in patients with SAA from the Transplant Outcomes in Aplastic Anemia (TOAA) study. All SAA patients received allogeneic HCT between 1989 to 2015; pre-HCT blood samples collected before conditioning were available at the Center for International Blood and Marrow Transplant Research (CIBMTR) biorepository. Telomere length was measured by qPCR. SNP-array data were used to calculate genetically predicted TL and detect mCAs across the genome.
The sample included 738 patients with acquired SAA. The median age at transplant/sample collection was 20.4 years old (range=0.2 to 77.4)) and 56.6% were male. SAA patients had shorter TL than expected for age (Median TL percentile-for-age: 35.7th (range=0.0 to 99.9)). Chromosomal alterations were detected in 211 patients (28.6%), with chr6p copy-neutral loss of heterogeneity and chr7-monosomy being the most common, affecting 15.9% and 3.0% of the patients, respectively. Fourteen percent of patients had mCA’s spanning the Major Histocompatibility Complex (MHC) class I and II. Patients with an alteration had shorter TL than those without (Median: 26.9 versus 38.7 percentile-for-age, p=0.02). This association remained statistically significant after adjusting for age and important clinical factors (Odds Ratio: 1.45, 95% Confidence Interval[1.02, 2.07]). Patients with an alteration cell fraction ≥40% (N=26) were over 4-times as likely to have short telomeres compared to those without an alteration.
In conclusion, patients with acquired SAA had shorter telomeres than expected for their age, and over a quarter harbored a chromosomal alteration. Short telomeres were associated with harboring an alteration. The insights derived from this cohort further the field of public health by improving our comprehension of hematological disease burden and dynamics.


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Item Type: Other Thesis, Dissertation, or Long Paper (Master Essay)
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Strauss, JoshuaJDS257@pitt.eduJDS257
ContributionContributors NameEmailPitt UsernameORCID
Committee ChairYuan, Jian-Minyuanj@pitt.eduyuanjUNSPECIFIED
Committee MemberGadalla, Shahinazgadallas@mail.nih.govUNSPECIFIEDUNSPECIFIED
Committee MemberIm, Annieimannie@pitt.eduimannieUNSPECIFIED
Date: 17 May 2023
Date Type: Completion
Submission Date: 20 April 2023
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 35
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Epidemiology
Degree: MPH - Master of Public Health
Thesis Type: Master Essay
Refereed: Yes
Uncontrolled Keywords: aplastic anemia, chromosomal mosaicism, telomere length, cell fraction, allogeneic bone marrow transplantation, genomics, copy neutral loss of heterozygosity
Date Deposited: 17 May 2023 15:40
Last Modified: 17 May 2023 15:40


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