Abstract
Myelodysplastic syndrome (MDS) can easily transform into acute myeloid leukemia (AML), a process which is often associated with clonal evolution and development of complex karyotypes. Deletion of 5q (del(5q)) is the most frequent aberration in complex karyotypes. This prompted us to analyze clonal evolution in MDS patients with del(5q). There were 1684 patients with low and intermediate-risk MDS and del(5q) with or without one additional cytogenetic abnormality, who were investigated cytogenetically in our department, involving standard karyotyping, fluorescence in situ hybridization (FISH) and multicolor FISH. We identified 134 patients (8%) with aspects of clonal evolution. There are two main routes of cytogenetic clonal evolution: a stepwise accumulation of cytogenetic events over time and a catastrophic event, which we defined as the occurrence of two or more aberrations present at the same time, leading to a sudden development of highly complex clones. Of the 134 patients, 61% underwent a stepwise accumulation of events whereas 39% displayed a catastrophic event. Patients with isolated del(5q) showed significantly more often a stepwise accumulation of events rather than a catastrophic event. The most frequent aberrations in the group of stepwise accumulation were trisomy 8 and trisomy 21 which were significantly more frequent in this group compared to the catastrophic event group. In the group with catastrophic events, del(7q)/-7 and del(17p)/-17 were the most common aberrations. A loss of 17p, containing the tumor suppressor gene TP53, was found significantly more frequent in this group compared to the group of stepwise accumulation. This leads to the assumption that the loss of TP53 is the driving force in patients with del(5q) who undergo a sudden catastrophic event and evolve into complex karyotypes.
Highlights
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective and dysplastic hematopoiesis and increased risk of transformation into acute myeloid leukemia (AML) [1,2]
We identified 1684 patients with low- and intermediate-risk MDS and del(5q) whom were investigated cytogenetically at our institute using standard karyotyping and fluorescence in situ hybridization (FISH) analyses
Clonal evolution is not frequent in patients with MDS and del(5q) but if it occurs, it often results in disease progression and the emergence of a complex karyotype [3,9]
Summary
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective and dysplastic hematopoiesis and increased risk of transformation into acute myeloid leukemia (AML) [1,2]. A complex karyotype, defined as at least three clonal aberrations, is detected in approximately 10% to 15% of MDS patients, and is associated with a very short median survival of less than 12 months and a high risk of transformation into AML [3,4,5,6]. The outcome of patients with del(5q) with or without an additional cytogenetic aberration depends on the presence of clonal evolution, cytopenia, and excess of blasts in the bone marrow, which subsequently worsens the outcome and increases the risk of transformation into AML [1,7,8]. In MDS, the modes of clonal evolution and the impact of potential “driver” lesions leading to disease progression and transformation to AML have remained largely unclear and mechanisms responsible for the induction of chromosomal instability and the development of complex karyotypes are still poorly understood. MDS with del(5q) is assumed to be a relatively genetically stable hematologic neoplasm, clonal evolution, even into complex karyotypes, occurs in a significant proportion of patients, which prompted us to further investigate clonal evolution in this subgroup
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call