Clinical course of patients with incidental finding of 20q‐ in the bone marrow without a morphologic evidence of myeloid neoplasm

Jawad, Majd D.; Shi, Min; Oliveira, Jennifer L.; Hoyer, James D.; Hook, C. Christopher; Go, Ronald S.

doi:10.1002/ajh.24347

Cited by 9 publications

(5 citation statements)

References 17 publications

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“…It is well‐known that a proportion of ICUS patients with abnormal karyotype are at risk of progression to a myeloid malignancy. Jawad et al reported that 15% of the patients with isolated loss of chromosome 20q progressed to a myeloid neoplasm . This phenomenon is also described in healthy elderly individuals with CHIP, where a minor subset develops a hematological cancer .…”

Section: Discussionmentioning

confidence: 90%

Mutations in idiopathic cytopenia of undetermined significance assist diagnostics and correlate to dysplastic changes

et al. 2016

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Cytopenia is common in the elderly population and etiology may be difficult to assess. Here, we investigated the occurrence of mutations in patients with idiopathic cytopenia of undetermined significance and the usefulness in improving diagnostics. We included 60 patients with persistent cytopenia > 6 months without definite diagnosis of hematological neoplasm after routine assessment. Bone marrow material underwent a blinded morphology review and DNA was sequenced with a targeted 20 gene panel representing the most commonly mutated genes in myelodysplastic syndrome. Thirty seven (62%) patients carried at least one mutation at inclusion, and of these 95% carried a mutation in TET2, ASXL1, SRSF2, or DNMT3A. The most commonly mutated gene was TET2 observed in 43% of all patients. During one to eight years follow-up seven patients progressed to a myeloid neoplasm and six of these had a detectable mutation at study entry. Median time to progression was 53 months (range 10-78), and at time of progression each patient had at least two mutations detected. Mutations in TP53 and NRAS were not present in patients at inclusion, but identified as secondary hits triggering progression. The morphology review was concordant in 68% of all cases, and 93% of the cases reclassified into the group "highly suspicious for MDS" had a mutation. All patients who had a concordant review "highly suspicious for MDS" had at least two mutations detected. Overall, we show that morphology examination is challenging in this heterogeneous group and targeted sequencing helps identify patients at risk of progression. Am. J. Hematol. 91:1234-1238, 2016. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 90%

Mutations in idiopathic cytopenia of undetermined significance assist diagnostics and correlate to dysplastic changes

et al. 2016

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“…Based on the presence or absence of cytopenia(s), these patients belong to either a nonneoplastic or preneoplastic category encompassing clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia(s) of undetermined significance 16,17 . The clinical outcome in patients with isolated del(20q) is generally indolent, but 10−25% ultimately develop MDS, MPN, MDS/MPN or AML 6,7,18 . The association of del(20q) with such a wide range of diseases and variable clinical outcomes clearly indicates the underlying genetic and biologic heterogeneity.…”

Section: Discussionmentioning

confidence: 99%

“…According to the WHO classification (fourth edition) 4 , isolated del(20q) is not considered a definitive evidence for MDS in patients with unexplained cytopenia in the absence of morphologic evidence for MDS 5 , which sometimes results in a diagnostic and therapeutic dilemma. Studies have shown variable clinical outcomes in patients with isolated del(20q) and about 10−25% of patients ultimately evolve into various MNs including AML 6,7 . However, the underlying pathogenic mechanisms associated with MN progression are largely unknown in isolated del(20q) patients.…”

Section: Introductionmentioning

confidence: 99%

The significance of genetic mutations and their prognostic impact on patients with incidental finding of isolated del(20q) in bone marrow without morphologic evidence of a myeloid neoplasm

Ravindran

Ketterling

et al. 2020

Blood Cancer J.

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Patients with a sole del(20q) chromosomal abnormality and without morphologic features of a myeloid neoplasm (MN) have shown variable clinical outcomes. To explore the potential risk stratification markers in this group of patients, we evaluated their genetic mutational landscape by a 35-gene MN-focused next-generation sequencing (NGS) panel and examined the association of mutations to progression of MNs. Our study included 56 patients over a 10-year period with isolated del(20q), of whom 23 (41.1%) harbored at least one mutation. With a median follow-up of 32.6 months (range: 0.1−159.1), 9 of 23 patients with mutation(s) progressed to MNs, while all 33 patients without mutations did not progress to MN. Kaplan−Meier survival analysis demonstrated the presence of mutation(s) as a significant risk factor for progression to MN (P < 0.0001). MN progression was strongly associated with the presence of non-DNMT3A/TET2/ASXL1 epigenetic modifiers and nonspliceosome mutations (P = 0.003). There was no significant difference among patients with and without MN progression with respect to the number of mutations, variant allele frequency, percentage of del(20q), and other clinical/laboratory variables. This study illustrates the underlying genetic heterogeneity and complexity of isolated del(20q), and underscores the prognostic value of NGS mutational analysis in these cases.

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“…The deletion of 20q occurs mainly in myeloid malignances, but rarely it is also observed in lymphoproliferative disorders including multiple myeloma [2] . Significant proportion of MM cases with 20q- has been associated with a myeloproliferative diseases and/or dysplastic changes of the hematopoietic tissue and the anomaly in most of these cases was found in the non-plasma cells [4] .…”

Section: Discussionmentioning

confidence: 99%

“…The deletion of the long arm of chromosome 20 is accepted as myeloid cytogenetic marker, because it is a common finding in myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and Philadelphia negative chronic myeloproliferative neoplasms [1] . Rarely, 20q- is also observed in B-lymphoproliferative diseases, including multiple myeloma (MM) [2] . The role of 20q- in MM especially as a sole anomaly in the karyotype is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Evidence of two different molecular mechanisms as a consequence of an isolated 20q- abnormality in a case of multiple myeloma accompanied with myelodysplastic syndrome

Mitev

2021

Leukemia Research Reports

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The deletion of the long arm of chromosome 20 is a characteristic cytogenetic marker of myeloid disorders. Rarely, it is also found in lymphoproliferative diseases, including multiple myeloma (MM). The role of 20q- in MM is not fully understood. In the cases of MM which co-exist with primary or therapy-related dysplasia, this anomaly is mostly linked to the occurrence of myeloid neoplasms. On the other hand 20q- is found as an isolated anomaly in cases with MM that have no dysplastic features or is not accompanied with other hematological diseases which suggests that the 20q deletion is also important for the development of MM. This report describes an isolated 20q- anomaly in a case of a light chain myeloma co-existing with myelodysplastic syndrome (MDS). Fluorescent in situ hybridization (FISH) experiments have demonstrated the presence in the patient's bone marrow of a basic clone (stemline) with deletion of the PTPRT gene (located at 20q13.11) and two sidelines: one with deletion of the PTPRT and MAPRE1 genes (located at 20q11.12) found in the mature granulocytes and one with deletion of PTPRT and duplication of MAPRE1 found in the myeloma cells. These data have indicated that 20q- has appeared in the multipotent precursor cells and affects both myeloid and lymphoid lineage by two different molecular mechanisms - one possibly related to the pathogenesis of the MDS and another to the pathogenesis of the MM.

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Clinical course of patients with incidental finding of 20q‐ in the bone marrow without a morphologic evidence of myeloid neoplasm

Cited by 9 publications

References 17 publications

Mutations in idiopathic cytopenia of undetermined significance assist diagnostics and correlate to dysplastic changes

Mutations in idiopathic cytopenia of undetermined significance assist diagnostics and correlate to dysplastic changes

The significance of genetic mutations and their prognostic impact on patients with incidental finding of isolated del(20q) in bone marrow without morphologic evidence of a myeloid neoplasm

Evidence of two different molecular mechanisms as a consequence of an isolated 20q- abnormality in a case of multiple myeloma accompanied with myelodysplastic syndrome

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