Therapy-related myeloid neoplasms - what have we learned so far?

Therapy-related myeloid neoplasms are neoplastic processes arising as a result of chemotherapy, radiation therapy, or a combination of these modalities given for a primary condition. The disease biology varies based on the etiology and treatment modalities patients receive for their primary condition. Topoisomerase II inhibitor therapy results in balanced translocations. Alkylating agents, characteristically, give rise to more complex karyotypes and mutations in p53. Other etiologies include radiation therapy, high-dose chemotherapy with autologous stem cell transplantation and telomere dysfunction. Poor-risk cytogenetic abnormalities are more prevalent than they are in de novo leukemias and the prognosis of these patients is uniformly dismal. Outcome varies according to cytogenetic risk group. Treatment recommendations should be based on performance status and karyotype. An in-depth understanding of risk factors that lead to the development of therapy-related myeloid neoplasms would help developing risk-adapted treatment protocols and monitoring patients after treatment for the primary condition, translating into reduced incidence, early detection and timely treatment.

Mutations in EZH2 are associated with poor prognosis for patients with myeloid neoplasms

EZH2 is a component of the polycomb repressive complex 2(PRC2),which is a highly conserved histone methyltransferase that methylates lysine 27 of histone 3.EZH2 mutations are associated with oncogenesis and progression of cancers.However,the relationship between the clinical outcome of patients with myeloid malignancies and EZH2 mutations is controversial.Therefore,we performed a meta-analysis of 8 studies(n Z 2243 patients)that evaluates the correlation between EZH2 mutations and overall survival(OS)in patients with myeloid neoplasms.EZH2 mutations were associated with significantly worse OS(hazard ratio[HR]Z 2.37,95%confidential interval(CI),1.48e3.79).In a word,EZH2 mutations indicate a poor prognosis for patients with myeloid neoplasms.

Acute myeloid leukemia in the era of precision medicine:recent advances in diagnostic classification and risk stratification

Acute myeloid leukemia(AML) is a genetically heterogeneous myeloid malignancy that occurs more commonly in adults, and has an increasing incidence, most likely due to increasing age. Precise diagnostic classification of AML requires clinical and pathologic information, the latter including morphologic, immunophenotypic, cytogenetic and molecular genetic analysis. Risk stratification in AML requires cytogenetics evaluation as the most important predictor, with genetic mutations providing additional necessary information. AML with normal cytogenetics comprises about 40%-50% of all AML, and has been intensively investigated. The currently used 2008 World Health Organization classification of hematopoietic neoplasms has been proposed to be updated in2016, also to include an update on the classification of AML, due to the continuously increasing application of genomic techniques that have led to major advances in our knowledge of the pathogenesis of AML. The purpose of this review is to describe some of these recent major advances in the diagnostic classification and risk stratification of AML.

Myeloid neoplasm with eosinophilia and rearrangement of plateletderived growth factor receptor beta gene in children: Two case reports

BACKGROUND Myeloid neoplasm(MN)with eosinophilia and rearrangement of platelet-derived growth factor receptor beta(PDGFRB)shows a good therapeutic response to imatinib in adults.MN is rarely found in children,and the efficacy of imatinib on pediatric patients remain unclear.CASE SUMMARY We report 2 pediatric cases diagnosed with MN with eosinophilia and PDGFRB rearrangement who were treated with imatinib.Case 1 was a 1-year-old girl admitted to the hospital because of“abdominal distension with hyperleukocytosis for 3 mo”.She had leukocytosis,anemia,and eosinophilia(the absolute eosinophil count(AEC)was 8960/μL),and her fluorescence in situ hybridization(FISH)test revealed that PDGFRB rearrangement was detected in 70%of 500 interphase cells.Case 2 was a 2-year-old girl admitted to the hospital because of“recurrent fever and rashes for 1 mo”.Her blood cell count showed an AEC of 3540/μL.The FISH test revealed that PDGFRB rearrangement was detected in 71%of 500 interphase cells.Both patients were diagnosed as MN with eosinophilia and PDGFRB rearrangement.Imatinib was added into their treatment regimen.As expected,complete hematologic remission was achieved after 1 mo of treatment,and symptoms disappeared.CONCLUSION Although MN with eosinophilia and PDGFRB rearrangement usually occurs in adults,it can be found in children.The therapeutic benefits of imatinib in these 2 pediatric patients were consistent with its reported effects in adult patients.