We investigated 15,542 patients with suspected BCR-ABL1- negative myeloproliferative or myelodysplastic/myeloproliferative neoplasm (including 359 chronic myelomonocytic leukemia) by a molecular marker set.
The BCR-ABL-negative chronic myeloproliferative disorders (CMPD) and myelodysplastic/myeloproliferative diseases (MDS/MPD) are a spectrum of related conditions for which the molecular pathogenesis is poorly understood.
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).
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).
Atypical CML should therefore be considered as a JAK2 negative chronic myeloid neoplasm that remains properly categorized, alongside chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia, within the WHO group of myelodysplastic/myeloproliferative neoplasms.
A biopsy of the ulcerative lesions finally led to the diagnosis of neutrophilic panniculitis, which was sustained by a hybrid myelodysplastic/myeloproliferative disorder like BCR-ABL1-negative atypical chronic myeloid leukaemia.
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.
CBL(mut) were more frequent in myelodysplastic/myeloproliferative neoplasms than myeloproliferative neoplasms (51 of 328, 15.5% vs. 12 of 291, 4.1%; P<0.001).
A further mutation screen of 187 patients with myelodysplastic/myeloproliferative neoplasms identified RUNX1 mutations in 27 (14%) and CEBPA mutations in seven (4%) patients.
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.
In summary, our study shows for the first time the evidence of recurrent somatic ETNK1 mutations in the context of myeloproliferative/myelodysplastic disorders.
To gain more insight into EZH2 pathology, we sought to genetically characterize a cohort of 41 EZH2-mutated MDS/MPN patients using targeted deep next-generation sequencing (NGS), colony-forming progenitor assays and transcriptome analysis.
Screening of a total of 614 individuals with myeloid disorders revealed 49 monoallelic or biallelic EZH2 mutations in 42 individuals; the mutations were found most commonly in those with myelodysplastic/myeloproliferative neoplasms (27 out of 219 individuals, or 12%) and in those with myelofibrosis (4 out of 30 individuals, or 13%).
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.
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.
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 JAK2V617F gene mutation; no FLT3 mutation has been found in JAK2-positive MPNs, suggesting that the mutations are mutually exclusive.
Atypical CML should therefore be considered as a JAK2 negative chronic myeloid neoplasm that remains properly categorized, alongside chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia, within the WHO group of myelodysplastic/myeloproliferative neoplasms.