Signature OncoChip™ | HemEssential™
Clinical Vignette
Acute myeloid leukemia with normal karyotype*
A 35-year-old male patient presented with fatigue and reported bruising without trauma. Workup included sending bone marrow aspirate for cytogenetics, flow cytometry, and pathology review. Pathology results indicated a diagnosis consistent with acute myeloid leukemia, unspecified subtype. Karyotype showed a normal male result with a note indicating that chromosome morphology was poor and that only large abnormalities could be excluded. Given the pathology results, a FISH panel including an MLL break-apart probe was chosen in an effort to detect aberrations in AML that may be missed by a poor resolution karyotype. Results suggested the presence of an MLL translocation, with 50% of cells indicating potential rearrangement. Metaphases were not available for FISH analysis, so the MLL partner was not clarified further by FISH.
Knowing that identification of the specific MLL partner can be critical for establishing prognosis and helpful in determining treatment, the cytogenetics lab ordered the OncoChip™ | HemEssential™ panel.3 They chose this panel because it specifically targets three of the most common MLL translocations and has the potential to identify translocations with up to 40 different MLL partners.1
The OncoChip™ | HemEssential™ testing identified aberrations in the MLL and MLLT3 genes, suggesting a t(9;11)(p22;q23) creating a fusion between MLL and MLLT3. This translocation is the most common MLL rearrangement in AML, particularly in AML-M5, which a review of pathology characteristics confirmed that the pathology was consistent with this patient’s findings.1-3 While typically MLL translocations are associated with poor prognosis, the MLLT3 translocation is typically associated with a better outcome in patients with de novo AML, particularly when patients are treated with intensive post-remission therapy.2,3For this patient, the OncoChip™ | HemEssential™ testing provided more objective, accurate, and precise cytogenetics results than standard karyotyping and FISH combined. As a result, the diagnosis was confirmed and the clinician was able to provide more specific prognostic information to the patient and modify therapy to maximize the likelihood of a good outcome.
Figure 1. OncoChip™ | HemEssential™ plots showing MLLT3/MLL translocation. The top panel shows an ideogram of chromosome 9 with the p-arm to the left and q-arm to the right. The section of chromosome indicated in red is expanded to show the plot of array CGH data for the 9p21.3 sub-band including MLLT3. The pink highlighted area within the plot indicates a peak delineating the translocation breakpoint within MLLT3. The bottom panel similarly shows an ideogram of chromosome 11 with the region below expanded to show the plot of array CGH data for the 11q23.3 sub-band including MLL. The pink highlighted area indicates a peak delineating the translocation breakpoint within MLL.
References:
- Meyer et al. 2009. Leukemia. 23:1490-9.
- Mitterbauer-Hohendanner and Mannhalter 2004. Eur J Clin Invest. 34 Suppl 2:12-24.
- Mrózek et al. 1997. Blood. 90:4532-8.
* This vignette is based upon a real patient, however specific details have been changed to demonstrate utility of the platform and protect patient privacy.