Bloom syndrome with myelodysplastic syndrome that was converted into acute myeloid leukaemia, with new ophthalmologic manifestations: the first report from Syria

Aljarad, Sara; Alhamid, Ahmad; Rahmeh, Ahmad Rami; Alibraheem, Abdelaziz; Wafa, Abdulsamad; Al‐Achkar, Walid; Aljarad, Ziad; Aziz, Ghasan

doi:10.1093/omcr/omy096

Cited by 5 publications

(3 citation statements)

References 11 publications

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“…The two nonresponders had congenital KMT2A ‐rearranged ALL with lineage switch after CAR‐T therapy and AML as a second malignancy in the setting of a DNA damage repair defect, respectively. In the literature, AML in patients with Bloom syndrome is uniformly fatal 20‐23 from either therapy‐related hypertoxicity or refractory disease.…”

Section: Discussionmentioning

confidence: 99%

Single‐center pediatric experience with venetoclax and azacitidine as treatment for myelodysplastic syndrome and acute myeloid leukemia

Winters

Maloney

Treece

et al. 2020

Pediatric Blood & Cancer

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Background The BCL‐2 inhibitor venetoclax (ven) has revolutionized the treatment of acute myeloid leukemia (AML) in elderly adults, leading to its recent FDA approval for this population in combination regimens. Although extensive data exist for adult myeloid malignancies, there are limited preclinical data on the efficacy and/or dosing of venetoclax for pediatric myelodysplastic syndrome (MDS) or AML and thus little information to guide use of this regimen in pediatric patients. Our objective was to describe our single‐center experience with venetoclax in combination with the hypomethylating agent 5‐azacitidine (aza) in pediatric patients with MDS or AML. Procedure We conducted a retrospective chart review of patients treated at Children's Hospital Colorado prior to March 2020 with at least one cycle of ven/aza. Patients were included if between the ages of 1 and 25 years with a diagnosis of high‐grade MDS or AML. AML patients had relapsed or primary refractory disease or were deemed poor candidates for standard chemotherapy. Results Eight patients received ven/aza, two for high‐grade MDS and six for AML. Ven/aza was well tolerated by all patients. The most common adverse events seen with this regimen were gastrointestinal and hematologic. Morphologic responses were seen in six patients including both patients with MDS. All four AML responders became minimal residual disease negative. Three responders have thus far proceeded to allogeneic hematopoietic stem cell transplant following ven/aza. Conclusions Our clinical experience suggests that ven/aza is a safe and promising regimen that should be further explored with late‐phase clinical trials.

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Section: Discussionmentioning

confidence: 99%

Single‐center pediatric experience with venetoclax and azacitidine as treatment for myelodysplastic syndrome and acute myeloid leukemia

Winters

Maloney

Treece

et al. 2020

Pediatric Blood & Cancer

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“…Patients with BSyn present with short stature, congenital telangiectatic erythema, and increased susceptibility to infections and cancer, most commonly leukemia, lymphoma, and colorectal cancer (Aktas et al, 2000 ; Aljarad et al, 2018 ; Bloom, 1954 ; Cunniff et al, 2017 ; Sugranes et al, 2022 ). Traditional anti‐cancer treatments that cause damage to DNA, such as chemotherapy and radiation, often result in severe life‐threatening toxicities and increased risk of secondary malignancies for patients with BSyn, warranting significant dose modifications from standard practice (Adams et al, 2013 ; Grasemann et al, 1998 ; Kataoka et al, 1989 ).…”

Section: Introductionmentioning

confidence: 99%

Bloom syndrome patients and mice display accelerated epigenetic aging

Lee,

Zhang,

Flanagan

et al. 2023

Aging Cell

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Bloom syndrome (BSyn) is an autosomal recessive disorder caused by variants in the BLM gene, which is involved in genome stability. Patients with BSyn present with poor growth, sun sensitivity, mild immunodeficiency, diabetes, and increased risk of cancer, most commonly leukemias. Interestingly, patients with BSyn do not have other signs of premature aging such as early, progressive hair loss and cataracts. We set out to determine epigenetic age in BSyn, which can be a better predictor of health and disease over chronological age. Our results show for the first time that patients with BSyn have evidence of accelerated epigenetic aging across several measures in blood lymphocytes, as compared to carriers. Additionally, homozygous Blm mice exhibit accelerated methylation age in multiple tissues, including brain, blood, kidney, heart, and skin, according to the brain methylation clock. Overall, we find that Bloom syndrome is associated with accelerated epigenetic aging effects in multiple tissues and more generally a strong effect on CpG methylation levels.

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“…It has also been reported in the literature that ALL and treatment-related AML developed in a girl with Bloom syndrome. The girl was previously reported to have a BLM c.3415C>T nonsense mutation, and a newly formed BLM frameshift c.1624delG mutation developed [18]. In this sense, there are insufficient studies supporting the role of BLM mutations in the development of AML.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of New Generation Sequencing (NGS)-Based Somatic Gene Variations and Real-Time Polymerase Chain Reaction (PCR)-Based Gene Fusions in Elderly and Young Acute Leukemia Patients: A Retrospective View

Erdoğdu,

Örenay-Boyacıoğlu,

Boyacıoğlu

et al. 2024

JPM

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Malignant diseases occurring in elderly patients follow a different course from younger patients and show different genetic structures. Therefore, in this retrospective study, the somatic gene variant profile and fusion gene profiles of elderly and young acute leukemia patients were determined to draw attention to the existing genetic difference, and the results were compared. In this study, the records of 204 acute leukemia patients aged 18+ who were referred to the Molecular Pathology Laboratory from the Hematology Clinic between 2018 and 2022 were reviewed retrospectively. Fusion gene detection in patients was performed with the HemaVision®-28Q Panel. The NGS Myeloid Neoplasms Panel was conducted using the MiniSEQ NGS platform according to the manufacturer’s protocol. When all cases are evaluated together, the most frequently diagnosed acute leukemia is acute myeloid leukemia (85.8%). Both groups had a similar fusion gene profile; however, the fusion burden was higher in the elderly group. When the groups were evaluated in terms of somatic gene variations, there were differences between the groups, and the variation load was higher in the elderly group. Considering the different somatic gene variation profiles, it is understood that the genetic structure of tumor cells is different in elderly patients compared to young cases.

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Bloom syndrome with myelodysplastic syndrome that was converted into acute myeloid leukaemia, with new ophthalmologic manifestations: the first report from Syria

Cited by 5 publications

References 11 publications

Single‐center pediatric experience with venetoclax and azacitidine as treatment for myelodysplastic syndrome and acute myeloid leukemia

Single‐center pediatric experience with venetoclax and azacitidine as treatment for myelodysplastic syndrome and acute myeloid leukemia

Bloom syndrome patients and mice display accelerated epigenetic aging

Evaluation of New Generation Sequencing (NGS)-Based Somatic Gene Variations and Real-Time Polymerase Chain Reaction (PCR)-Based Gene Fusions in Elderly and Young Acute Leukemia Patients: A Retrospective View

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