[1369] Acute Myeloid Leukemia, Not Otherwise Specified, with Minimal Differentiation: TDT+ and TDT- Subsets Have Distinctive Features

FA Khokhar, T Muzzafar, CE Bueso-Ramos, LJ Medeiros. MD Anderson Cancer Center, Houston, TX; St. Elizabeth Hospital, Beaumont, TX

Background: Acute myeloid leukemia (AML), minimally differentiated (M0) is defined as an AML with no evidence of myeloid differentiation by morphology and cytochemistry, and carries a poor prognosis with low remission rate. Runx1 (AML1) mutations have been identified in a subset of cases, and a recent gene expression profiling study has shown that TDT expression highly correlates with Runx 1 mutation and can be used as a surrogate for Runx1 mutation status (Silva et al. Blood 114: 3001, 2009). The goal of this study was to review our cases of AML-M0, subdivided according to TDT expression.
Design: 41 cases of AML-M0 were identified in our departmental files (2004-2008), and were analyzed by cytochemistry, flow cytometric immunophenotyping(FCI), conventional cytogenetics(CG) and molecular studies.

Table 1: Demographics and Clinical Presentation
Age (yrs) (m)WBC (K/uL) (m)% PB Blasts (m)% BM blasts (m)*Pre-existing / concurrent findings
TDT + (n=11)718.771841/11 (9%)
TDT – (n=30)622.2246114/30 (47%)
*MDS, MPN or Multilineage dysplasia. (m=median)

Table 2: Molecular, CG and FCI Findings
FLT3Chr 5Chr 7Chr 13Chr 17CD15 – flowMPO – flow
TDT + (n=11)3/10 (30%)0/11 (0%)2/11 (18%)4/11 (36%)1/11 (9%)4/4 (100%)1/9 (11%)
TDT – (n=30)1/28 (3%)11/30 (37%)10/30 (33%)2/30 (6%)6/30 (20%)8/12 (66%)3/24 (12%)

Results: There were 27 men and 14 women with a median age of 64 years (range 16-87). TDT+ (FCI) cases were more likely to have a higher bone marrow (BM) blast %age (student's t test), more frequent FLT3 mutations and chromosome (chr) 13 abnormalities. TDT- cases were more likely to have history/concurrent myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN) or multilineage dysplasia and chr 5 abnormalities by CG (Fischer's exact test).
Conclusions: Based on TdT expression, AML with minimal differentiation can be divided into two distinct groups. The TDT+ subset, which has been shown to correlate with RUNX1 mutations, is similar to acute lymphoblastic leukemia in that these patients are more likely to have higher BM blast %age at presentation as well as chr 13 abnormalities, in accord with known positive correlation between FLT3 expression and RUNX1mutation (FLT3 gene is located on chr 13). The TDT- cohort is less distinctive but appears to be more often associated with or arises on a background of MDS or MPN with complex cytogenetics.
Category: Hematopathology

Wednesday, March 24, 2010 1:00 PM

Poster Session VI # 183, Wednesday Afternoon


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