Monosomal karyotype (MK) in myeloid malignancies
2011-04-01 Maria Gomes da Silva , Joana Perdigão Affiliation1.Laboratorio de Hemato-Oncologia - Seccao de Citogenetica, Instituto Portugues de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal
Clinics and Pathology
Disease
Acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), primary myelofibrosis (PMF)
Epidemiology
In AML, the frequency of monosomal karyotype increases with age: 4% in patients ≤ 30 years; 6-10% in patients ≤ 60 years and 13-20% above 60 years.
The frequency of MK cases is significantly higher in t-AML compared with de novo AML (24% vs 10%).
In MDS, MK frequency among patients with a complex karyotype is 83%. In children with advanced MDS MK frequency is 15%.
In PMF patients, MK is present in 42% of complex karyotype cases.
The frequency of MK cases is significantly higher in t-AML compared with de novo AML (24% vs 10%).
In MDS, MK frequency among patients with a complex karyotype is 83%. In children with advanced MDS MK frequency is 15%.
In PMF patients, MK is present in 42% of complex karyotype cases.
Clinics
Monosomal karyotype is associated with prior chemotherapy or history of abnormal blood counts (Estey, 2010).
Prognosis
Very poor prognosis, worse with advanced age.
In comparison with non-MK patients, AML, MDS and PMF patients with a monosomal karyotype have lower overall survival rates. In MDS and PMF, the risk of leukemic transformation is higher in MK patients than in patients with non-MK complex karyotypes.
In MK-AML, overall survival at 4 years after diagnosis is 3-4% (vs 26-27% for non-CBF, non-MK AML patients) and event-free survival 2%. Overall survival decreases with advancing age: 17-40% for patients ≤ 30 years, 3-4% ≤ 60 years and 1% in patients older than 60 years. Complete remission rate is generally low, and also worse in older groups (24-52% under 60 years and 13-34% in patients older than 60 years).
In adult MDS patients with MK, 2-year survival is 6% (vs 23% for complex karyotype without monosomies) and 1-year leukemia risk is 32% (vs 14% for complex karyotype without monosomies). In advanced childhood MDS, the presence of a MK does not seem to be an independent adverse prognostic factor.
In PMF, the median survival for MK patients is 6 months, 2-year survival rate is 17% and 2-year leukemic transformation rate is 29% (vs 24 months, 51% and 8,3% in complex karyotype without monosomies).
As with most prognostic factors, the significance of monosomal karyotype seems to depend on the treatment strategy (Itzykson et al., 2011; Löwenberg et al., 2011).
In comparison with non-MK patients, AML, MDS and PMF patients with a monosomal karyotype have lower overall survival rates. In MDS and PMF, the risk of leukemic transformation is higher in MK patients than in patients with non-MK complex karyotypes.
In MK-AML, overall survival at 4 years after diagnosis is 3-4% (vs 26-27% for non-CBF, non-MK AML patients) and event-free survival 2%. Overall survival decreases with advancing age: 17-40% for patients ≤ 30 years, 3-4% ≤ 60 years and 1% in patients older than 60 years. Complete remission rate is generally low, and also worse in older groups (24-52% under 60 years and 13-34% in patients older than 60 years).
In adult MDS patients with MK, 2-year survival is 6% (vs 23% for complex karyotype without monosomies) and 1-year leukemia risk is 32% (vs 14% for complex karyotype without monosomies). In advanced childhood MDS, the presence of a MK does not seem to be an independent adverse prognostic factor.
In PMF, the median survival for MK patients is 6 months, 2-year survival rate is 17% and 2-year leukemic transformation rate is 29% (vs 24 months, 51% and 8,3% in complex karyotype without monosomies).
As with most prognostic factors, the significance of monosomal karyotype seems to depend on the treatment strategy (Itzykson et al., 2011; Löwenberg et al., 2011).
Genes Involved and Proteins
Note
Genes involved are unknown.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 21454879 | 2011 | Acute myeloid leukemia with monosomal karyotype at the far end of the unfavorable prognostic spectrum. | Breems DA et al |
| 18695255 | 2008 | Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. | Breems DA et al |
| 21239839 | 2010 | High cytogenetic or molecular genetic risk acute myeloid leukemia. | Estey E et al |
| 20802024 | 2010 | Complex karyotype newly defined: the strongest prognostic factor in advanced childhood myelodysplastic syndrome. | Göhring G et al |
| 20385793 | 2010 | Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. | Grimwade D et al |
| 21468040 | 2011 | Prognostic significance of monosomal karyotype in higher risk myelodysplastic syndrome treated with azacitidine. | Itzykson R et al |
| 21127174 | 2011 | The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML. | Kayser S et al |
| 21410371 | 2011 | Cytarabine dose for acute myeloid leukemia. | Löwenberg B et al |
| 20562328 | 2010 | Prognostic impact of monosomal karyotype in young adult and elderly acute myeloid leukemia: the Southwest Oncology Group (SWOG) experience. | Medeiros BC et al |
| 21072042 | 2011 | Monosomal karyotype in myelodysplastic syndromes, with or without monosomy 7 or 5, is prognostically worse than an otherwise complex karyotype. | Patnaik MM et al |
| 21450904 | 2011 | Monosomal karyotype in primary myelofibrosis is detrimental to both overall and leukemia-free survival. | Vaidya R et al |
Summary
Note
Monosomal karyotype is defined as the presence of at least 2 autosomal monosomies or a single autosomal monosomy associated with at least one structural abnormality.
Citation
Maria Gomes da Silva ; Joana Perdigão
Monosomal karyotype (MK) in myeloid malignancies
Atlas Genet Cytogenet Oncol Haematol. 2011-04-01
Online version: http://atlasgeneticsoncology.org/haematological/1574/monosomal-karyotype-(mk)-in-myeloid-malignancies
