Genetic Testing Improves Treatments, Outcomes in MPNs and MDS


Patients with MDS/MPN unclassifiable, whose genes were found to be the most heterogeneous, had a different molecular landscape that was comparable with those observed within other MDS/MPN.

Genetic Testing Improves Treatments, Outcomes in MPNs and MDS

Genetic Testing Improves Treatments, Outcomes in MPNs and MDS

Mutually exclusive gene combinations were observed between specific subtypes of patients with myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs) and most other types of MDS/MPNs that have an impact on patient outcomes, including TET2-SRSF2 in chronic myelomonocytic leukemia (CMML), ASXL1-SETBP1 in atypical chronic myeloid leukemia (aCML), or SF3B1-JAK2 in MDS/MPN with ring sideroblasts and thrombocytosis (MPN-RS-T), according to results of a recent analysis.1,2

In the study, researchers from the MDS Group of the Josep Carreras Leukaemia Research Institute and Munich Leukemia Laboratory (MLL), identified pieces of the mutational landscape of and the exclusive gene combinations specific to MDS and MPNs. The study was performed in concurrence with an international effort by MLL called the 5000 Genomes Project, which recruited 5000 patients with hematological neoplasms to undergo whole-genome and transcriptome sequencing.

“In previous studies, over 90% of MDS/MPN harbored somatic mutations in a group of known genes, which are related to their pathophysiological features and play a role in their clinical heterogeneity, but none of them was specific of MDS/MPN,” lead study author Laura Palomo, MSc, PhD candidate in the Genetics and Epigenetics in Myeloid Neoplasms Group with Josep Carreras Leukaemia Research Institute, stated in a press release. “In our study, made with whole-genome data from a cohort of 367 patients with MDS/MPN, we identified genotype-phenotype associations and potential diagnostic and prognostic molecular markers that could translate to medical practice. We also wanted to provide novel insights into the clonal hierarchy of mutations of MDS/MPN.”

Patients with MDS/MPN unclassifiable (MPN-U), whose genes were found to be the most heterogeneous, had a different molecular landscape that was comparable with those observed within other MDS/MPN subtypes—which investigators believe that this may have impacted the patients who were studied.

In the analysis, investigators explored a cohort of 367 patients with MDS/MPN and performed genomic sequencing in order to better understand the mutational landscape of this patient population. Patients had a variety of overlapping diseases, including CMML (n = 119), aCML (n = 71), MDS/MPN-RS-T (n = 71), and MDS/MPN-U (n = 106). Thirty recurrently mutated genes were observed in at least 3% of patients. Investigators noted differences in recurrently mutated gene distribution and clonal architecture between the different MDS/MPN subtypes.

Results indicated that patients with CMML, aCML, and MDS/MPN-RS-T had recurrent mutation combinations that were exclusive to their disease. Although patients with MDS/MPN-U were observed as having overlapping heterogeneous features, it is worth noting that they can still be classified according to their molecular profile, the investigators stated.

Current diagnostics that help with MDS/MPN include complete blood counts with differential, peripheral blood smear, blood chemistry studies, and bone marrow aspiration and biopsy.3 Once a tissue sample is retrieved, additional laboratory tests can take place, such as cytogenetic analysis or identifying the sample's immunocytochemistry. The delivery of results can be impacted by turnaround time, and therefore delay treatment. Therefore, if this type of genetic testing were incorporated into clinical practice, the turnaround process could be expedited.

By identifying the molecular landscape of patients with MDS/MPN, the investigators concluded that they were able to confirm that specific gene mutations have the ability to impact different subgroups within this population.


1. 2020 July 2 Identified the genetic landscape of Myelodysplastic/Myeloproliferative Neoplasms. [News release]. Josep Carreras Leukaemia Research Institute. July 2, 2020. Accessed 2. July 7, 2020.

3. Palomo L, Meggendorfer M, Hutter S, et al. Molecular landscape and clonal architecture of adult myelodysplastic/myeloproliferative neoplasms. Blood. Published June 23, 2020. doi:10.1182/blood.2019004229. Accessed July 7, 2020.

4. PDQ® Adult Treatment Editorial Board. PDQ Myelodysplastic/ Myeloproliferative Neoplasms Treatment. National Cancer Institute. Updated October 30, 2019. Accessed July 7, 2020.

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