Signature OncoChip™ | B-cell ALL Panel 2
Clinical Vignette
Determining prognosis in acute lymphoblastic leukemia when standard cytogenetic methods do not provide an answer **
A 17-year-old male presented with a 3-week history of fatigue, weakness, nausea, and bone pain. There was no lymph node enlargement or organomegaly on exam. Initial workup showed a hemoglobin of 11.7 g/dL and thrombocytopenia with a platelet count of 57 x 109/L. Bone marrow aspirate showed extensive infiltration with 55% blasts. B-cell markers CD10, CD19, and CD22 were expressed, and surface Ig expression was positive. Based on morphology and immunophenotyping, a diagnosis of precursor B-cell acute lymphoblastic leukemia (B-ALL) was made. Bone marrow chromosomes were ordered to provide confirmation of the diagnosis and potentially define prognosis; however, after 3 days of attempting cell culture, no metaphase cells were visible. A FISH panel for common aberrations in pediatric ALL was performed on the interphase nuclei, with probes targeting translocations involving BCR/ABL1, ETV6/RUNX1, MLL, and PBX1/TCF3 and enumerating chromosomes 4, 10, and 17. FISH testing was completed 3 days later with normal results. Knowing that cytogenetic abnormalities can play an important role in prognosis for patients with pediatric ALL, the cytogeneticist ordered the OncoChip™ | B-cell ALL Panel 2 because this test can detect less frequently seen translocations in ALL that had not been covered by the FISH panel. 1
Results of the OncoChip testing were reported on the 5th day after receiving the specimen. The OncoChip™ | B-ALL Panel 2 testing identified aberrations in the IGH and BCL2 genes, suggesting a t(14;18)(q32;q21) that juxtaposes the two gene regions, resulting in deregulation of BCL2.2 This translocation is rarely seen in patients with ALL and has been associated with an extremely poor prognosis in this disease.3 Because of the dismal prognosis associated with this translocation in ALL patients, the patient’s treatment was immediately changed to a more intensive chemotherapy regimen.
For this patient, the OncoChip™ | B-cell ALL Panel 2 as a reflex to normal FISH results provided cytogenetic results critical to prognosis that would not have otherwise been obtained. Additionally, had the OncoChip™ | B-cell ALL Panel 2 been ordered at diagnosis in combination with the OncoChip™ | B-cell ALL Panel 1 or as a reflex to it, results would have been available more quickly, adding valuable time for treatment for this patient. Because of the results obtained, the clinician was able to act quickly to alter therapy based on the important prognostic information provided by this test.
Figure 1. OncoChip™ | B-cell ALL Panel 2 plots showing IGH/BCL2 translocation.The top panel shows an ideogram of chromosome 14 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 14q32.33 sub-band including part of the IGH gene. The pink highlighted area within the plot indicates a peak delineating the translocation breakpoint within IGH. The blue highlighted area within the plot indicates a deletion adjacent to the translocation breakpoint. The bottom panel similarly shows an ideogram of chromosome 18 with the region below expanded to show the plot of array CGH data for the 18q21.33 sub-band including BCL2. The pink highlighted area indicates a peak delineating the translocation breakpoint within BCL2.
References:
- Pui et al. 2004. NEJM 350:1535-48.
- Dyer et al. 2010. Blood 115:1490-9.
- D’Achille et al. 2006. Cancer Genet Cytogenet. 171:52-56.
* As of the date of publishing (07/13/2011) two of the translocations targeted by this assay have been validated according to Signature Genomics’ standard validation procedures. Please contact Signature Genomics for the latest validation information.
** This vignette is based upon a real patient, however specific details have been changed to demonstrate utility of the platform and protect patient privacy.