Diagnosis of acute myeloid leukemia according to the WHO classification in the Japan Adult Leukemia Study Group AML-97 protocol

Abstract

We reviewed and categorized 638 of 809 patients who were registered in the Japan Adult Leukemia Study Group acute myeloid leukemia (AML)-97 protocol using morphological means. Patients with the M3 subtype were excluded from the study group. According to the WHO classification, 171 patients (26.8%) had AML with recurrent genetic abnormalities, 133 (20.8%) had AML with multilineage dysplasia (MLD), 331 (51.9%) had AML not otherwise categorized, and 3 (0.5%) had acute leukemia of ambiguous lineage. The platelet count was higher and the rate of myeloperoxidase (MPO)-positive blasts was lower in AML with MLD than in the other WHO categories. The outcome was significantly better in patients with high (≥50%) than with low (<50%) ratios of MPO-positive blasts (P < 0.01). The 5-year survival rates for patients with favorable, intermediate, and adverse karyotypes were 63.4, 39.1, and 0.0%, respectively, and 35.5% for those with 11q23 abnormalities (P < 0.0001). Overall survival (OS) did not significantly differ between nine patients with t(9;11) and 23 with other 11q23 abnormalities (P = 0.22). Our results confirmed that the cytogenetic profile, MLD phenotype, and MPO-positivity of blasts are associated with survival in patients with AML, and showed that each category had the characteristics of the WHO classification such as incidence, clinical features, and OS.

Clinical characterization of acute myeloid leukemia with myelodysplasia-related changes as defined by the 2008 WHO classification system

“…Among 65 patients with intermediate-risk cytogenetics, the outcome difference between the AML-MRC and AML-NOS remained significant (OS, P ϭ .029; PFS, P ϭ .023), also indicating prognostic significance of multilineage dysplasia. This confirms the previously observed clinical significance of multilineage dysplasia, [6][7][8] when strictly defined by the WHO criteria.…”

“…The percentage of patients encompassed by the AML-MRC category was 48%, compared with prior reports of AML with multilineage dysplasia comprising 24% to 38%. [6][7][8]18 Overall, 26 patients had an NPM1 mutation (16 were FLT3 mutated), 25 had FLT3-ITD alone, 8 had FLT3-D835 alone, and 9 had a CEBPA mutation (3 were FLT3 mutated). The frequency of these mutations is within the range of prior studies.…”

“…As it relates to AML, this includes limited cytogenetic findings, presence of morphologic dysplasia, and prior therapy. 5 Although later studies have validated this system, [6][7][8] including the importance of multilineage dysplasia, others have suggested that multilineage dysplasia correlates with unfavorable cytogenetics and has no independent impact on prognosis. 9,10 In 2008, a revision of the WHO classification has incorporated recently acquired genetic information into an updated classification scheme of AML.…”

MLL Gene Alterations in Acute Myeloid Leukaemia (11q23/MLL+ AML)

“…The amplification of genes, a common occurrence in a wide range of tumors, is rarely observed in acute leukemia. Gene amplification is identified in approximately 1% of patients with AML by conducting a cytogenetic analysis in the form of dmin (the area of the MLL gene) [50].…”

New Possible Targetable Genes for Future Treatment of Mixed Lineage Leukemia

“…The gene is also accompanied by MLL partner proteins which form a protein complex which can alter epigenetic profiles [9] and activate preleukemic target genes which are key for leukemogenesis, including HOXA9, MEIS1 [10]. Although pediatric and adult AML patients show common properties, the differences have not yet been identified between MLL and AML [11]. Leukemia genomic abnormalities arise cytogenetic problems, which need different therapy and methods.…”