title: TdT expression in acute myeloid leukemia with minimal differentiation is associated with distinctive clinicopathological features and better overall survival following stem cell transplantation.
abstract: The diagnostic criteria for acute myeloid leukemia (AML), not otherwise specified, with minimal differentiation (AML-M0, French-American-British classification), have been refined in the 2008 World Health Organization (WHO) classification. Terminal deoxynucleotidyl transferase (TdT) expression in AML-M0 has been proposed by others as a surrogate for RUNX1 (runt-related transcription factor 1) mutations, a mutation associated with distinct gene expression profiles in AML-M0. In this study, we investigated the significance of TdT expression in AML-M0 cases defined using the 2008 WHO classification criteria. Demographic, laboratory and clinical information were obtained from the hospital medical records. Statistical analysis was performed using Student's t-test, log-rank test and Fisher's exact test. The study group included 30 AML-M0 patients (male:female=19:11; median age: 60 years). In all, 10 cases of AML-M0 were positive for TdT(+) and 20 cases were negative for TdT(-). Patients with TdT+ AML-M0 had higher peripheral blood and bone marrow blast counts compared to patients with TdT- AML-M0 (P=0.01). TdT expression in AML-M0 was not associated with a distinct immunophenotype. Monoclonal IgH and TCR gene rearrangements were frequent, but independent of TdT expression in AML-M0. TdT expression in AML-M0 correlated with trisomy 13 and inversely correlated with aberrations of chromosomes 5 and 17. Among six patients with AML-M0 who received a stem cell transplant, overall survival was significantly longer for the three TdT+ patients compared with the three TdT- patients (P=0.03). In the TdT+AML-M0 subgroup, the three patients with stem cell transplant had better overall survival compared with five patients who did not receive stem cell transplant (P=0.01). We conclude that AML-M0, as currently defined in the 2008 WHO classification, can be divided into two groups based on TdT expression. Although there is a need to assess a greater number of patients, our results suggest that TdT positivity in AML-M0 identifies a subset of patients with a better prognosis after stem cell transplant.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Keyur P
authors.initials: KP
authors.lastname: Patel
authors.forename: Faisal A
authors.initials: FA
authors.lastname: Khokhar
authors.forename: Tariq
authors.initials: T
authors.lastname: Muzzafar
authors.forename: M
authors.initials: M
authors.lastname: James You
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Bueso-Ramos
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.forename: Sherrie
authors.initials: S
authors.lastname: Pierce
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004253:DNA Nucleotidylexotransferase / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D033581:Stem Cell Transplantation; D015996:Survival Rate
chemical_list: D004253:DNA Nucleotidylexotransferase