CD146 Molecule Expression in B Cells Acute Lymphoblastic Leukemia (B-ALLs): A Flow-Cytometric Marker for an Accurate Diagnostic Workup

Abstract

Background: 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.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Acute Lymphoblastic Leukemia (ALL); CD13; CD146; CD33; Flow-cytometry; Ph Chromosome; Ph-like ALLs.

Figure 1

Representative plots of the flow gating strategies to detect CD146+in Ph+ B common patient. Leukemic B cells were gated within the total CD45+ leukocyte population, then CD146+/CD19+ leukemic cells were identified in CD34+ population. CD34+/CD146+/CD19+/CD10+/CD66c+/CD13+/CD33+/CD38− cells are depicted in red, residual B lymphocytes are depicted in blue while residual granuloblast in green.