Laganà Alessandro, Totaro Matteo, Bisegna Maria Laura, Elia Loredana, Intoppa Stefania, Beldinanzi Marco, Matarazzo Mabel, di Trani Mariangela, Costa Alessandro, Maglione Raffaele, Mandelli Biancamaria, Chiaretti Sabina, Martelli Maurizio, De Propris Maria Stefania
Hematology, Department of Translational and Precision Medicine, Sapienza University, 00161 Rome, Italy.
Hematology Unit, Businco Hospital, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Mediterr J Hematol Infect Dis. 2024 Sep 1;16(1):e2024064. doi: 10.4084/MJHID.2024.064. eCollection 2024.
B-lineage acute lymphoblastic leukemias (B-ALL) harboring the t(9;22)(q34;q11)/BCR::ABL1 rearrangement represent a category with previously dismal prognosis whose management and outcome dramatically changed thanks to the use of tyrosine kinase inhibitors (TKIs) usage and more recently full chemo-free approaches. The prompt identification of these cases represents an important clinical need.
We sought to identify an optimized cytofluorimetric diagnostic panel to predict the presence of Philadelphia chromosome (Ph) in B-ALL cases by the introduction of CD146 in our multiparametric flow cytometry (MFC) panels.
We prospectively evaluated a total of 245 cases of newly diagnosed B-ALLs with a CD146 positivity threshold >10% referred to the Division of Hematology of 'Sapienza' University of Rome. We compared the results of CD146 expression percentage and its mean fluorescence intensity (MFI) between Ph+ ALLs, Ph-like ALLs, and molecularly negative ALLs.
Seventy-nine of the 245 B-ALL cases (32%) did not present mutations at molecular testing, with 144/245 (59%) resulting in Ph+ ALL and 19/245 (8%) Ph-like ALLs. Comparing the 3 groups, we found that Ph+ B-ALLs were characterized by higher expression percentage of myeloid markers such as CD13, CD33, and CD66c and low expression of CD38; Ph+ B-ALL showed a higher CD146 expression percentage and MFI when compared with both molecular negative B-ALL and Ph-like ALLs; neither the mean percentage of CD146 expression neither CD146 MFI were statically different between molecular negative B-ALL and Ph-like ALLs.
Our data demonstrate the association between CD146 expression and Ph+ ALLs. CD146, along with myeloid markers, may help to identify a distinctive immunophenotypic pattern, useful for rapid identification in the diagnostic routine of this subtype of B-ALLs that benefits from a specific therapeutic approach.
携带t(9;22)(q34;q11)/BCR::ABL1重排的B系急性淋巴细胞白血病(B-ALL)曾是预后极差的一类疾病,由于酪氨酸激酶抑制剂(TKIs)的使用以及最近出现的完全无化疗方法,其治疗和预后发生了巨大变化。及时识别这些病例是一项重要的临床需求。
我们试图通过在多参数流式细胞术(MFC)检测中引入CD146,确定一种优化的细胞荧光诊断方法,以预测B-ALL病例中费城染色体(Ph)的存在。
我们前瞻性评估了罗马“萨皮恩扎”大学血液科收治的245例新诊断的B-ALL病例,CD146阳性阈值>10%。我们比较了Ph+ ALL、Ph样ALL和分子学阴性ALL之间CD146表达百分比及其平均荧光强度(MFI)的结果。
245例B-ALL病例中,79例(32%)在分子检测中未发现突变,144/245例(59%)为Ph+ ALL,19/245例(8%)为Ph样ALL。比较这3组病例,我们发现Ph+ B-ALL的特征是髓系标志物如CD13、CD33和CD66c的表达百分比更高,而CD38表达较低;与分子学阴性B-ALL和Ph样ALL相比,Ph+ B-ALL的CD146表达百分比和MFI更高;分子学阴性B-ALL和Ph样ALL之间的CD146表达平均百分比和CD146 MFI均无统计学差异。
我们的数据证明了CD146表达与Ph+ ALL之间的关联。CD146与髓系标志物一起,可能有助于识别一种独特的免疫表型模式,有助于在诊断常规中快速识别这种受益于特定治疗方法的B-ALL亚型。