Mutations of signal-induced proliferation-associated gene 1 (<i>SIPA1</i>), a RAP1 GTPase-activating protein, were reported in patients with juvenile myelomonocytic leukemia, a childhood myelodysplastic/myeloproliferative neoplasm (MDS/MPN).
Mutations of signal-induced proliferation-associated gene 1 (<i>SIPA1</i>), a RAP1 GTPase-activating protein, were reported in patients with juvenile myelomonocytic leukemia, a childhood myelodysplastic/myeloproliferative neoplasm (MDS/MPN).
Four patients had myelodysplastic/myeloproliferative neoplasm-like marrow changes such as hypercellularity, increased myeloid to erythroid ratio, numerous micromegakaryocytes (highlighted by CD42b), and marrow fibrosis.
Somatic SETBP1 mutations were identified by whole exome sequencing in several phenotypes of myelodysplastic/myeloproliferative neoplasms (MDS/MPN), including atypical chronic myeloid leukemia, chronic myelomonocytic leukemia, and juvenile myelomonocytic leukemia as well as in secondary acute myeloid leukemia (sAML).
As the third documented case successfully treating aCML with ruxolitinib, this case highlights the importance of prompt CSF3R sequencing analysis for myeloproliferative and myelodysplastic/myeloproliferative neoplasms.
According to the 2008 WHO classification, the category of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) includes atypical chronic myeloid leukaemia (aCML), chronic myelomonocytic leukaemia (CMML), MDS/MPN-unclassifiable (MDS/MPN-U), juvenile myelomonocytic leukaemia (JMML) and a "provisional" entity, refractory anaemia with ring sideroblasts and thrombocytosis (RARS-T).
When adding CD56 or CD7 labeling to the Ogata score, sensitivity rose to 66% for low-risk myelodysplastic syndromes, to 89% for myelodysplastic/myeloproliferative neoplasms and to 97% for refractory anemia with excess of blasts.
By molecular cytogenetics and direct sequencing, we searched for USB1 deletions/duplications and point mutations in 141 bone marrow DNA samples from patients with myelodysplastic syndromes (n = 126), myelodysplastic/myeloproliferative neoplasms (n = 12) and acute myeloid leukaemia (n = 3).
In summary, our study shows for the first time the evidence of recurrent somatic ETNK1 mutations in the context of myeloproliferative/myelodysplastic disorders.
The technique is demonstrated here for the evaluation of epigenetic heterogeneity at p14(ARF) and BRCA1 gene-promoter loci in liquid biopsies obtained from patients in association with non-small cell lung cancer (NSCLC) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN), respectively.
Previous studies have reported FLT3 mutation in as many as 9.2% of myeloproliferative neoplasms (MPNs) and myelodysplastic/myeloproliferative neoplasms (MDS/MPNs), as well as in chronic myelogenous leukemia, that are negative for the JAK2 V617F gene mutation; no FLT3 mutation has been found in JAK2-positive MPNs, suggesting that the mutations are mutually exclusive.
Refractory anemia with ring sideroblasts (RARS-T) associated with marked thrombocytosis is a myelodysplastic/myeloproliferative neoplasm associated with both SF3B1 and JAK2 or MPL mutations.
Analysis of other transcription factors known to be frequently mutated in acute myeloid leukemia revealed NPM1 mutations in six (3%) and WT1 mutations in two (1%) patients with myelodysplastic/myeloproliferative neoplasms.
A further mutation screen of 187 patients with myelodysplastic/myeloproliferative neoplasms identified RUNX1 mutations in 27 (14%) and CEBPA mutations in seven (4%) patients.
PDGFRB, a transmembrane tyrosine kinase receptor for platelet-derived growth factor, is constitutively activated by gene fusion with different partners in myeloproliferative/myelodysplastic disorders with peculiar clinical characteristics.
PDGFRB, a transmembrane tyrosine kinase receptor for platelet-derived growth factor, is constitutively activated by gene fusion with different partners in myeloproliferative/myelodysplastic disorders with peculiar clinical characteristics.
Two myeloid neoplasms defined by the presence of RS, include refractory anemia with ring sideroblasts (RARS), now classified under myelodysplastic syndromes with RS (MDS-RS) and RARS with thrombocytosis (RARS-T); now called myelodysplastic/myeloproliferative neoplasm with RS and thrombocytosis (MDS/MPN-RS-T).