Rare germline variant contributions to myeloid malignancy susceptibility

Li, Samuel T; Wang, Janet; Wei, Ruipeng; Shi, Ruqi; Ademà, Vera; Nagata, Yasunobu; Kerr, Cassandra M; Kuzmanovic, Teodora; Przychodzen, Bartlomiej; Solé, Françesc; Maciejewski, Jaroslaw P.; LaFramboise, Thomas

doi:10.1038/s41375-019-0701-8

Cited by 8 publications

(5 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, we showed that in case of allogenic HSC transplantations, analysis on DNA from skin fibroblasts are required. These results are concordant with methodology used by other authors, such as Churpek et al (21) and Li et al (22) who used either skin biopsy, T-lymphocytes from blood, or buccal swab to affirm germline nature of the detected variants. Our initial workflow thus retrospectively appeared unappropriated to patients that are being evaluated for HM predisposition.…”

Section: Discussionsupporting

confidence: 90%

Hereditary predisposition to malignant myeloid hemopathies: Caution in use of saliva and guideline based on our experience

Perani

Bourthoumieu²,

Rizzo³

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

BackgroundPredisposition to myeloid malignancies is a field at the border of hematology and genetics. Knowledge in this domain has so rapidly increased that WHO defined in 2016 the new “Myeloid Neoplasms with Germline Predisposition” category of tumors. High throughput sequencing is frequently performed in tumors either for diagnosis or prognosis, but this approach may identify potential germline variants that have to be confirmed on non-infiltrated tissues.MethodIn this study, we systematically compared NGS data from genetic analysis performed on all sample types (bone marrow, blood, saliva, skin fibroblasts and hair follicles) in 29 patients, and 44 of their relatives (blood and saliva).ResultsWe showed that saliva was usable for relatives, but only for 24% (7/29) of our patients. Most of patients’ saliva were either “non-contributive” (14/29 i.e., 48% because clearly or probably infiltrated) or “inconclusive” (8/29 corresponding to 28%).ConclusionThe recommendations for the use of saliva we present here focus on the importance of collecting saliva during remission when possible. Moreover, we propose hair follicles as an alternative to skin biopsy, that remains the gold standard especially in case of allogenic hematopoietic stem cells transplantation. Technological progresses have revolutionized the diagnosis of predisposition to solid or hematological malignancies, and it is very likely that new techniques will help to manage the familial predisposition in the future.

show abstract

Section: Discussionsupporting

confidence: 90%

Hereditary predisposition to malignant myeloid hemopathies: Caution in use of saliva and guideline based on our experience

Perani

Bourthoumieu²,

Rizzo³

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…The BMF cohort included 321 CCF and 29 MLL cases. The MN cohort consisted of 686 CCF, 1074 MLL, and 898 open-data cases [11,[15][16][17][18]. Research studies were performed after obtaining written informed consents in accordance with the protocols approved by the respective Institutional Review Boards (IRBs) and ethic committees.…”

Section: Patients and Materialsmentioning

confidence: 99%

“…Based on the increased prevalence of GL alterations in adult patients [8,9], we suspect that the role of hereditary factors in the pathogenesis of adult BMF and MN is greatly underestimated. We previously estimated the frequency of rare GL variants in BMF and MN cases [10,11]. However, the panel used in our previous studies included only a small number of genes.…”

Section: Introductionmentioning

confidence: 99%

Significance of hereditary gene alterations for the pathogenesis of adult bone marrow failure versus myeloid neoplasia

Kubota

Zawit²,

Durrani³

et al. 2022

Leukemia

Self Cite

View full text Add to dashboard Cite

Broader genetic screening has led to the growing recognition of the role of germline variants associated with adult bone marrow failure (BMF) and myeloid neoplasia (MN) not exclusively in children and young adults. In this study, we applied a germline variant panel to 3008 adult BMF and MN cases to assess the importance of germline genetics and its impact on disease phenotype and prognosis. In our cohort, up to 9.7% of BMF and 5.3% of MN cases carried germline variants. Our cohort also included heterozygous carriers of recessive traits, suggesting they contribute to the risk of BMF and MN. By gene category, variants of Fanconi anemia gene family represented the highest-frequency category for both BMF and MN cases, found in 4.9% and 1.7% cases, respectively. In addition, about 1.4% of BMF and 0.19% of MN cases harbored multiple germline variants affecting often functionally related genes as compound heterozygous. The burden of germline variants in BMF and MN was clearly associated with acquisition of monosomy 7. While BMF cases carrying germline variants showed similar overall survival as compared to the wild-type (WT) cases, MN cases with germline variants experienced a significantly shorter overall survival as compared to WT cases.

show abstract

“…Another challenge for clinical laboratories is bridging the genomic information with other clinical features of leukemias. Germline variants are not always detectable for all leukemias, and there are ongoing studies aiming to gain more precise information on the subject ( 80 , 81 ). Clinical evaluation and use of these tests are challenging because of the lack of familiarity with this type of testing, the requirement for DNA samples that reasonably approximate the germline state and absence of standardization across the different brands of diagnostic platforms for genes that are sequenced as well as their capabilities for detection of full range of variants ( 82 ).…”

Section: Challenges Aheadmentioning

confidence: 99%

Comparison of Laboratory Methods for the Clinical Follow Up of Checkpoint Blockade Therapies in Leukemia: Current Status and Challenges Ahead

et al. 2022

View full text Add to dashboard Cite

The development of immune checkpoint inhibitors, the monoclonal antibodies that modulate the interaction between immune checkpoint molecules or their ligands on the immune cells or tumor tissue has revolutionized cancer treatment. While there are various studies proving their efficacy in hematological malignancies, there is also a body of accumulating evidence indicating that immune checkpoint inhibitors’ clinical benefits are limited in such diseases. In addition, due to their regulatory nature that balances the immune responses, blockade of immune checkpoints may lead to toxic side effects and autoimmune responses, and even primary or acquired resistance mechanisms may restrict their success. Thus, the need for laboratory biomarkers to identify and monitor patient populations who are more likely respond to this type of therapy and the management of side effects seem critical. However, guidelines regarding the use of immune checkpoint inhibitors in hematological cancers and during follow-up are limited while there is no consensus on the laboratory parameters to be investigated for safety and efficacy of the treatment. This review aims to provide an insight into recent information on predictive and prognostic value of biomarkers and laboratory tests for the clinical follow up of hematological malignancies, with an emphasis on leukemia.

show abstract

Rare germline variant contributions to myeloid malignancy susceptibility

Cited by 8 publications

References 93 publications

Hereditary predisposition to malignant myeloid hemopathies: Caution in use of saliva and guideline based on our experience

Hereditary predisposition to malignant myeloid hemopathies: Caution in use of saliva and guideline based on our experience

Significance of hereditary gene alterations for the pathogenesis of adult bone marrow failure versus myeloid neoplasia

Comparison of Laboratory Methods for the Clinical Follow Up of Checkpoint Blockade Therapies in Leukemia: Current Status and Challenges Ahead

Contact Info

Product

Resources

About