Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Division of Laboratory Genetics, Mayo Clinic, Rochester, MN, USA.
Histopathology. 2020 Jun;76(7):1042-1054. doi: 10.1111/his.14097. Epub 2020 May 17.
Rearrangement of the platelet-derived growth factor receptor B (PDGFRB) gene defines a unique group of myeloid/lymphoid neoplasms with frequent eosinophilia and high sensitivity to tyrosine kinase inhibitors. This genetic abnormality is also rarely reported in Philadelphia-like B-cell acute lymphoblastic leukaemia/lymphoma (B-ALL). PDGFRB rearrangement was initially thought to only occur in cases with 5q31-33 rearrangement as determined with conventional cytogenetics; however, there are reported cases with cryptic rearrangements. We aim to develop a broader strategy for screening of PDGFRB rearrangements of patients with myeloid/lymphoid neoplasms.
We performed fluorescence in-situ hybridisation (FISH) for PDGFRB rearrangement in 197 patients, including 70 with B-ALL, 10 with myeloid neoplasms with 5q31-33 rearrangements, and 117 with eosinophilia (≥0.5 × 10 /l in peripheral blood or ≥5% in bone marrow), and identified PDGFRB rearrangement in four of 197 (2.0%) cases. In an attempt to identify clinicopathological and genetic features that may have a stronger association with PDGFRB rearrangement, we analysed 13 patients with confirmed PDGFRB rearrangements, including 10 with myeloid neoplasms and three with B-ALL. Among the 10 patients with myeloid neoplasms, eosinophilia was present in eight, monocytosis in two, 5q31-33 rearrangement in seven, and abnormal bone marrow morphology in all. All patients with myeloid neoplasms showed an excellent response to imatinib, including a patient in blast crisis. The three B-ALL patients presented de novo, showed no eosinophilia, had a complex karyotype including 5q31-33 rearrangement, and had clinically aggressive courses with ultimate patient demise.
These findings suggest that a higher yield for the identification of PDGFRB rearrangement may result from an index of suspicion in patients with eosinophilia, monocytosis, bone marrow features of a myeloid neoplasm, and 5q31-33 rearrangement, and patients with Philadelphia-like B-ALL.
血小板衍生生长因子受体 B（PDGFRB）基因重排定义了一组独特的髓系/淋系肿瘤，这些肿瘤常伴有嗜酸性粒细胞增多和对酪氨酸激酶抑制剂高度敏感。这种遗传异常在费城样 B 细胞急性淋巴细胞白血病/淋巴瘤（B-ALL）中也很少见报道。PDGFRB 重排最初被认为仅发生在常规细胞遗传学确定的 5q31-33 重排的病例中；然而，也有报道称存在隐匿性重排。我们旨在开发一种更广泛的策略，用于筛查髓系/淋系肿瘤患者的 PDGFRB 重排。
我们对 197 例患者进行了 PDGFRB 重排的荧光原位杂交（FISH）检测，其中包括 70 例 B-ALL、10 例伴有 5q31-33 重排的髓系肿瘤和 117 例嗜酸性粒细胞增多症（外周血中≥0.5×109/L 或骨髓中≥5%），并在 197 例患者中发现了 4 例（2.0%）PDGFRB 重排。为了确定可能与 PDGFRB 重排具有更强关联的临床病理和遗传特征，我们分析了 13 例经证实存在 PDGFRB 重排的患者，其中包括 10 例髓系肿瘤和 3 例 B-ALL。在 10 例髓系肿瘤患者中，8 例伴有嗜酸性粒细胞增多症，2 例伴有单核细胞增多症，7 例伴有 5q31-33 重排，所有患者均伴有骨髓形态异常。所有伴有髓系肿瘤的患者均对伊马替尼有良好的反应，包括一例处于急变期的患者。3 例 B-ALL 患者均为初发，无嗜酸性粒细胞增多症，均具有复杂的核型，包括 5q31-33 重排，且临床病程具有侵袭性，最终患者死亡。
这些发现表明，在伴有嗜酸性粒细胞增多症、单核细胞增多症、骨髓髓系肿瘤特征和 5q31-33 重排的患者以及具有费城样 B-ALL 的患者中，通过提高对 PDGFRB 重排的怀疑指数，可能会获得更高的 PDGFRB 重排识别率。
