Yumei Chen

Identification of functional cooperative mutations of SETD2 in human acute leukemia

Acute leukemia characterized by chromosomal rearrangements requires additional molecular disruptions to develop into full-blown malignancy, yet the cooperative mechanisms remain elusive. Using whole-genome sequencing of a pair of monozygotic twins discordant for MLL (also called KMT2A) gene–rearranged leukemia, we identified a transforming MLL-NRIP3 fusion gene and biallelic mutations in SETD2 (encoding a histone H3K36 methyltransferase). Moreover, loss-of-function point mutations in SETD2 were recurrent (6.2%) in 241 patients with acute leukemia and were associated with multiple major chromosomal aberrations. We observed a global loss of H3K36 trimethylation (H3K36me3) in leukemic blasts with mutations in SETD2. In the presence of a genetic lesion, downregulation of SETD2 contributed to both initiation and progression during leukemia development by promoting the self-renewal potential of leukemia stem cells. Therefore, our study provides compelling evidence for SETD2 as a new tumor suppressor. Disruption of the SETD2-H3K36me3 pathway is a distinct epigenetic mechanism for leukemia development.

Retrospective analysis of 65 Chinese children with acute promyelocytic leukemia: A single center experience

There are very limited data reported about childhood acute promyelocytic leukemia (APL), especially with arsenic trioxide (As2O3) treatment. We review the clinical course and treatment outcome of 65 children APL.

Transient pancytopenia preceding T lineage acute lymphoblastic leukemia.

Transient pancytopenia preceding acute lymphoblastic leukemia (pre-ALL) is a rare occurrence usually affecting children with subsequent development of B lineage ALL. We report a case of pre-ALL characterized by a T cell immunophenotype and abnormal karyotype t (11; 14) (q10; q10). The patient achieved a transient complete remission after initial therapy, but relapsed within a few months and died of leukemic encephalopathy. To the best of our knowledge, this is the first report of T lineage pre-ALL.

The role of standard-dose cytarabine in children with acute promyelocytic leukemia: a single-center experience.

Background There are very limited data reported about the role of cytarabine (Ara-C) in childhood acute promyelocytic leukemia (APL). We review the clinical course and treatment outcome of APL and explore the role of standard-dose Ara-C for children. Procedure Between January 1999 and December 2008, 36 children (<14 y) with newly diagnosed APL were included. Results The overall complete remission rate was 97.2% (35/36). Two patients were lost to follow-up after induction. Two groups of patients were identified according to different consolidation chemotherapy regimens. Seventeen patients were given polychemotherapy in combination with standard-dose Ara-C (group I), 16 patients were given daunorubicin alone (group II). Although the 5-year estimate of disease-free survival between groups I and II had no statistically significant difference (P=0.614), there was a 12% higher disease-free survival rate for group I. Conclusion Standard-dose Ara-C might play some role in the consolidation treatment of children suffering from APL.

Whole exome sequencing identifies novel mutations of epigenetic regulators in chemorefractory pediatric acute myeloid leukemia

Genomic alterations underlying chemotherapy resistance remains poorly characterized in pediatric acute myeloid leukemia (AML). In this study, we used whole exome sequencing to identify gene mutations associated with chemo-resistance in 44 pediatric AML patients. We identified previously unreported mutations involving epigenetic regulators such as KDM5C, SRIT6, CHD4, and PRPF6 in pediatric AML patients. Despite low prevalence in general pediatric AML, mutations involving epigenetic regulators including splicing factors, were collectively enriched as a group in primary chemo-resistance AML patients. In addition, clonal evolution analysis of secondary chemo-resistance AML patients reveals dominant clone at diagnosis could survive several course of intensified chemotherapy. And gain of new mutations in genes such as MVP, TCF3, SS18, and BCL10, may contribute to chemo-resistance at relapse. These results provide novel insights into the genetic basis of treatment failure in pediatric AML.

FLT3 pathway is a potential therapeutic target for PRC2 mutated T cell acute lymphoblastic leukemia

TO THE EDITOR: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, and T-cell ALL (T-ALL) accounts for approximately 15% of cases of childhood ALL.[1][1],[2][2] Early T-cell precursor ALL (ETP-ALL) is a recently recognized subtype of T-ALL.[3][3],[4][4] Hallmarks of T-ALL