Although the clinical features of the Isocitrate dehydrogenase 2 (IDH2) mutation in acute myeloid leukemia (AML) have been characterized, its prognostic significance remains controversial and its stability has not been investigated. We analyzed 446 adults with primary non-M3 AML and found IDH2 R172, R140 and IDH1 R132 mutations occurred at a frequency of 2.9, 9.2 and 6.1%, respectively. Compared with wild-type IDH2, mutation of IDH2 was associated with higher platelet counts, intermediate-risk or normal karyotype and isolated þ 8, but was inversely correlated with expression of HLA-DR, CD34, CD15, CD7 and CD56, and was mutually exclusive with WT1 mutation and chromosomal translocations involving core-binding factors. All these correlations became stronger when IDH1 and IDH2 mutations were considered together. Multivariate analysis revealed IDH2 mutation as an independent favorable prognostic factor. IDH2 À /FLT3-ITD þ genotype conferred especially negative impact on survival. Compared with IDH2 R140 mutation, IDH2 R172 mutation was associated with younger age, lower white blood cell count and lactate dehydrogenase level, and was mutually exclusive with NPM1 mutation. Serial analyses of IDH2 mutations at both diagnosis and relapse in 121 patients confirmed high stability of IDH2 mutations. In conclusion, IDH2 mutation is a stable marker during disease evolution and confers favorable prognosis.

Conventionally, acute myeloid leukemia (AML) patients are categorized into good-, intermediate- and poor-risk groups according to cytogenetic changes. However, patients with intermediate-risk cytogenetics represent a largely heterogeneous population regarding treatment response and clinical outcome. In this study, we integrated cytogenetics and molecular mutations in the analysis of 318 patients with de novo non-M3 AML who received standard chemotherapy. According to the mutation status of eight genes, including NPM1, CEBPA, IDH2, RUNX1, WT1, ASXL1, DNMT3A and FLT3, that had prognostic significance, 229 patients with intermediate-risk cytogenetics could be refinedly stratified into three groups with distinct prognosis (P<0.001); patients with good-risk genotypes had a favorable outcome (overall survival, OS, not reached) similar to those with good-risk cytogenetics, whereas those with poor-risk genotypes had an unfavorable prognosis (OS, 10 months) similar to those with poor-risk cytogenetics (OS, 13.5 months), and the remaining patients with other genotypes had an intermediate outcome (OS, 25 months). Integration of cytogenetic and molecular profiling could thus reduce the number of intermediate-risk AML patients from around three-fourth to one-fourth. In conclusion, integration of cytogenetic and molecular changes improves the prognostic stratification of AML patients, especially those with intermediate-risk cytogenetics, and may lead to better decision on therapeutic strategy.

Recently, mutations of the additional sex comb-like 1 (ASXL1) gene were identified in patients with myelodysplastic syndrome (MDS), but the interaction of this mutation with other genetic alterations and its dynamic changes during disease progression remain to be determined. In this study, ASXL1 mutations were identified in 106 (22.7%) of the 466 patients with primary MDS based on the French-American-British (FAB) classification and 62 (17.1%) of the 362 patients based on the World Health Organization (WHO) classification. ASXL1 mutation was closely associated with trisomy 8 and mutations of RUNX1, EZH2, IDH, NRAS, JAK2, SETBP1 and SRSF2, but was negatively associated with SF3B1 mutation. Most ASXL1-mutated patients (85%) had concurrent other gene mutations at diagnosis. ASXL1 mutation was an independent poor prognostic factor for survival. Sequential studies showed that the original ASXL1 mutation remained unchanged at disease progression in all 32 ASXL1-mutated patients but were frequently accompanied with acquisition of mutations of other genes, including RUNX1, NRAS, KRAS, SF3B1, SETBP1 and chromosomal evolution. On the other side, among the 80 ASXL1-wild patients, only one acquired ASXL1 mutation at leukemia transformation. In conclusion, ASXL1 mutations in association with other genetic alterations may have a role in the development of MDS but contribute little to disease progression.

No abstract

Retinoic acid (RA) syndrome is a life-threatening side-effect of value lower than that of Latino patients but higher than that of ATRA. Factors that predict the development of this syndromeItalians. Leukemic cells from four patients showed coexalso remain to be determined. pression of T cell-associated antigen CD2 which was highlyIn this report, we described the clinical and biological of APL were collected at our institute according to FrenchKeywords: acute promyelocytic leukemia; all-trans retinoic acid; American-British (FAB) classification; 15 they accounted for retinoic acid syndrome; PML-RAR␣ fusion transcript 15% of total de novo acute myeloid leukemia (AML). The diagnosis was confirmed in all cases by the presence of t(15;17) in conventional cytogenetic study and/or PML-RAR␣ Introduction fusion transcript in reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Acute promyelocytic leukemia (APL) is a specific subtype of Oral ATRA of 45 mg/m 2 /day was prescribed to all 25 cases acute myeloid leukemia (AML) characterized by the unique who were treated at our institute. It was used for 30-90 days morphology of leukemic cells and by the specific chromodepending on the clinical response. Complete blood cell somal translocation t(15;17) which results in a novel fusion counts, white cell classification, profiles of coagulopathy, biotranscript PML-RAR␣ (retinoic acid receptor ␣ chain). Three chemistry, electrolytes, and side-effects of ATRA were forms of PML-RAR␣ fusion transcript, long (L), short (S), and recorded. RA syndrome was defined as the presence of unexvariant (V) forms, had been detected by molecular studies, plained fever, respiratory distress, pleuropericardial effusion, corresponding to the breakpoints of PML gene in intron 6, pulmonary infiltrate, and weight gain after the start of ATRA. 16 intron 3 and exon 6, respectively. 1 The proportion of these No concurrent full-dose chemotherapy was used even in three forms of fusion transcript varied in different geographic patients who presented with or developed leukocytosis during areas. 2-6 Coexpression of T cell-associated antigen CD2 on ATRA treatment. When RA syndrome occurred, intravenous the leukemic cells was detected in some APL patients and was dexamethasone 10 mg was administered intravenously for 3-found to be closely related to S form transcript in some 5 days twice a day without discontinuing ATRA. Three reports, 7,8 but not in others. 9 patients (cases 6,12 and 21) received leukapheresis or lowAll-trans retinoic acid (ATRA) could induce a complete dose hydroxyurea when RA syndrome occurred; all of them presented with high initial and peak peripheral white blood cell (WBC) count. CR was defined as normal marrow cellu- and Hb Ͼ12 g/dl) as previously described. 17