Monosomal karyotype in myeloid neoplasias: a literature review

Anelli, Luisa; Pasciolla, Crescenza; Zagaria, Antonella; Specchia, Giorgina; Albano, Francesco

doi:10.2147/ott.s133937

Cited by 13 publications

(8 citation statements)

References 58 publications

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“…The consideration of monosomal karyotype as a more accurate risk factor than karyotype complexity in MDS and AML has been controversial [9]. First, not all studies agree on the effect of MK on survival [6, 7, 10]. Second, the vast majority of studies examining the prognostic impact of MK in MDS did not evaluate TP53 mutation status or HC, missing these potential confounders strongly associated with MK [8, 12, 37].…”

Section: Discussionmentioning

confidence: 99%

“…The types of abnormalities present, co-occurring somatic mutations, and clinical features all contribute to the actual risk in patients with complex karyotypes. Several groups have examined the prognostic impact of a monosomal karyotype (MK), defined as a complete loss of an autosomal chromosome in the presence of at least one other structural abnormality or additional monosomy, as in practice, most patients with MK also have CK [6]. Parsing complex karyotypes as monosomal can identify MDS patients with even greater risk than predicted by tools like the IPSS-R, although the independent prognostic significance of MK is still debated [7–12].…”

Section: Introductionmentioning

confidence: 99%

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TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups

Haase¹,

Stevenson²,

Neuberg³

et al. 2019

Leukemia

196

158

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Risk stratification is critical in the care of patients with myelodysplastic syndromes (MDS). Approximately 10% have a complex karyotype (CK), defined as more than two cytogenetic abnormalities, which is a highly adverse prognostic marker. However, CK-MDS can carry a wide range of chromosomal abnormalities and somatic mutations. To refine risk stratification of CK-MDS patients, we examined data from 359 CK-MDS patients shared by the International Working Group for MDS. Mutations were underrepresented with the exception of TP53 mutations, identified in 55% of patients. TP53 mutated patients had even fewer co-mutated genes but were enriched for the del(5q) chromosomal abnormality ( p < 0.005), monosomal karyotype ( p < 0.001), and high complexity, defined as more than 4 cytogenetic abnormalities ( p < 0.001). Monosomal karyotype, high complexity, and TP53 mutation were individually associated with shorter overall survival, but monosomal status was not significant in a multivariable model. Multivariable survival modeling identified severe anemia (hemoglobin < 8.0 g/dL ), NRAS mutation, SF3B1 mutation, TP53 mutation, elevated blast percentage (>10%), abnormal 3q, abnormal 9, and monosomy 7 as having the greatest survival risk. The poor risk associated with CK-MDS is driven by its association with prognostically adverse TP53 mutations and can be refined by considering clinical and karyotype features.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups

Haase¹,

Stevenson²,

Neuberg³

et al. 2019

Leukemia

196

158

View full text Add to dashboard Cite

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“…Monosomy 7 is commonly seen as a secondary genetic lesion in patients with AML with inv(3)(q21.3q26.2) and is associated with an even poorer prognosis in this already poor prognostic group. 4 One study suggests the presence of monosomy 7 in AML with inv(3)(q21.3q26.2) may also increase the risk of DI and may represent a unique disease 5 and patients affected may need surveillance for DI.…”

Section: Discussionmentioning

confidence: 99%

Acute myeloid leukaemia presenting with diabetes insipidus

Bardin

Ritchie

McLachlan

et al. 2019

Internal Medicine Journal

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A 41‐year‐old man was diagnosed with hypogonadotropic hypogonadism managed with gonadotropins after routine fertility review. Eight months later he presented with new polydipsia and polyuria, lethargy and easy bruising. A full blood count showed 28% circulating blasts. A bone marrow biopsy confirmed a diagnosis of acute myeloid leukaemia with inv(3)(q21.3q26.2) with additional monosomy 7. Central diabetes insipidus (DI) was diagnosed following a water deprivation test. Pituitary magnetic resonance imaging showed a slightly thickened pituitary stalk, stable Rathke’s cyst, and new absence of the pituitary bright spot. The patient was commenced on desmopressin and induction chemotherapy, subsequently requiring a bone marrow transplant. Bone marrow examination at 100 days post‐transplant revealed cytogenetic remission. All symptoms of DI resolved and magnetic resonance imaging showed return of the posterior bright spot and a pituitary stalk of normal thickness. Biochemical hypogonadotropic hypogonadism persisted but was uninterpretable in the context of systemic illness and recent chemotherapy. DI is a rare complication of haematological malignancies, and the prevalence and pathophysiology of DI in this context are poorly understood. Pathogenic mechanisms proposed include leukaemic infiltration of the pituitary, interference with antidiuretic hormone synthesis, and abnormal thrombopoiesis influencing hormone levels. Particular cytogenetic abnormalities such as inv(3)(q21.3q26.2) and monosomy 7 appear to be more commonly associated with DI and also appear to confer worse outcomes. Aetiologies in the literature remain elusive but as DI is a recognised association of haematological malignancies it should be considered in a patient presenting with polydipsia and polyuria.

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“…In this study, three or more chromosomal abnormalities were defined as complex karyotype 3 (CK3). The monosomal karyotype (MK) was defined as the presence of a chromosomal aberration pattern characterized by at least two autosomal monosomies or one monosomy plus one or more structural aberrations (not including loss of a chromosome) 6,7 . Subclones (SC) were defined as the presence of one to three subclones 8 …”

Section: Methodsmentioning

confidence: 99%

“…In addition to MC, complex karyotype (CK), monosomal karyotype (MK), and subclones (SC) are considered to result from genomic instability. CK and MK have been established as independent chromosomal prognostic factors 1,6‐8 and are used clinically.…”

Section: Introductionmentioning

confidence: 99%

Marker chromosome is a strong poor prognosis factor after allogeneic HSCT for adverse‐risk AML patients

Fuse

Tanaka

Shibasaki

et al. 2020

European J of Haematology

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Chromosome analysis is necessary for the diagnosis and risk classification of acute myeloid leukemia (AML). 1,2 Fragmented chromosomes whose origin cannot be identified from an existing autosomal or sex chromosome may be observed, termed marker chromosome (MC). MC is considered to originate from marked genomic instability. 3 It is a relatively common abnormality, and its incidence in AML was reported to be 6.6%-16.1%. 4,5 However, MC is currently not specifically considered in the risk classifications by the refined Medical Research Council (rMRC) 1 or European Leukemia Net (ELN). 2 Although AML with MC (MC+) has a poor prognosis even after intensive chemotherapy, 4,5 its influence on the outcome after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is unclear.

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Monosomal karyotype in myeloid neoplasias: a literature review

Cited by 13 publications

References 58 publications

TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups

TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups

Acute myeloid leukaemia presenting with diabetes insipidus

Marker chromosome is a strong poor prognosis factor after allogeneic HSCT for adverse‐risk AML patients

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