The BCR-ABL1 rearrangement found in hematologic malignancies such as chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). About 5-10% of patients with CML and ALL lack cytogenetic evidence of the Ph chromosome detected only by fluorescence in situ hybridization (FISH) and/or reverse transcription-polymerase chain reaction (RT-PCR) without any cytogenetic evidence of Ph chromosome. Here we describe a patient with Ph-negative ALL and a FISH-negative cryptic BCR-ABL1 rearrangement, as confirmed by RT-PCR and sequencing analyses. A 20-year-old female with Down syndrome and relapsed ALL was referred to our hospital. All 20 metaphase cells analyzed had a karyotype by conventional methods of 47, XX, +21 and FISH analysis yielded a signal for BCR-ABL1 consistent with a normal pattern. However, multiplex RT-PCR revealed an atypical band indicating the possibility of BCR-ABL1 translocation, which was confirmed by Split-out PCR, real-time PCR and direct sequencing. We revealed that this patient has a dual transcription of typical b3a2 and atypical b2a2 resulted from partial duplication of BCR exon 13, combined with ABL1 exon 2. Although cryptic BCR-ABL1 rearrangements are rare, they affect treatment regimens, making them clinically important. Precise molecular work up along with standard diagnostic tools used to detect BCR-ABL1 rearrangements are recommended for these patients.Citation: Lee N, Lee H, Sohn J, et al. A patient with philadelphia-negative acute lymphoblastic leukemia with a FISH-negative cryptic BCR-ABL1 rearrangement detected by PCR and sequencing analysis.
Granulocyte colony-stimulating factor (G-CSF) is widely used as a neutrophil supportive therapy in cancer chemotherapy. Recently, some cases of G-CSF-induced aortitis are reported. Our case patient is a 54-year-old female diagnosed with breast cancer and received adjuvant chemotherapy with prophylactic use of G-CSF. She developed G-CSF-induced aortitis 20 days after the use of G-CSF. The disease was diagnosed with serum markers and radiologic findings. Her symptoms and imaging findings were rapidly improved with high-dose steroid therapy. The rapid improvement of the disease implies that prompt diagnosis with treatment can prevent severe vascular complications.
Background: Angiogenesis is important in proliferation and survival of neoplastic cells in multiple myeloma (MM). Microvessel density (MVD) is a useful angiogenesis marker, which can be detected by anti-CD34 immunohistochemical stain. However, counting the MVD of bone marrow (BM) by light microscopy has a limitation in standardization due to inter-observer differences. Consistent method for MVD assessment has been required to resolve the variation in number. Here we developed the MVD counting method using computerized image analyzer (CIA) and light microscopy.
Methods: A total of 21 patients with primary diagnosed with MM were evaluated. MVD was assessed by screening three hot spots of CD34 positive vessels on BM biopsy section (x40 magnification). MVD was measured by three different ways. First, the number of vessels was counted using light microscope at the time of diagnosis by several hematopathologists (MVD-A). Second, the total count of microvessels per 14435.2 μm2 (1388 × 1040μm) of marrow area was measured by a Zeiss microscope using AxioVison LE Image Analyzer with developed image analyzer program (MVD-B). In addition, manual count of captured image by CIA with one observer was examined (MVD-C). Software was developed using Microsoft visual studio (ver. 2010, Microsoft, USA) and VTK (ver. 5.10.0, Kitware, USA) library. Captured image was labeled via pre-processing for image enhancement and seed region growing algorithm to detect the MVD candidates. Using histogram texture analysis, each candidate was determined to MVD.
Results: The range of MVD was as followings: MVD-A (range 3-52; mean 16.5; SD 12.8), MVD-B (range 4-38; mean 19.6; SD 10.0), and MVD-C (range 5-34; mean 14.8; SD 7.8).There was a significant correlation between theses angiogenesis parameters. Pearson's correlation coefficient of MVD-A with MVD-B was 0.535 (P = 0.01), MVD-A with MVD-C was 0.581 (P < 0.01), and MVD-B with MVD-C was 0.897 (P < 0.01).
Conclusions: We developed the computer aided diagnostic tools to measure MVD more objectively. MVD count using image analyzer was well correlated with manual count and more accurate than MVD count on light microscope. Further studies with continuous upgrades on counting program are now in progress. Finally, we tried to apply this method in practice to predict the prognostic impact on MM patient at the time of diagnosis.
Citation Format: Kong Sun-Young, Nuri Lee, Young Jae Kim, Ji Yeon Sohn, Hyewon Lee, Hyeon-Seok Eom, Kwang Gi Kim. New computerized image analyzing technique for analysis of bone marrow microvessel density in multiple myeloma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 220. doi:10.1158/1538-7445.AM2015-220
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