CD146 MOLECULE EXPRESSION IN B CELLS ACUTE LYMPHOBLASTIC LEUKEMIA (B-ALLs): A FLOW- CYTOMETRIC MARKER FOR AN ACCURATE DIAGNOSTIC WORK-UP

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Alessandro Laganà
Matteo Totaro
Maria Laura Bisegna
Loredana Elia
Stefania Intoppa
Marco Beldinanzi
Mabel Matarazzo
Mariangela di Trani
Alessandro Costa
Raffaele Maglione
Biancamaria Mandelli
Sabina Chiaretti
Maurizio Martelli
Maria Stefania De Propris

Keywords

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

Abstract

Background: B-lineage acute lymphoblastic leukemias (B-ALL) harboring the t(9;22)(q34;q11)/BCR::ABL1rearrangement, 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-ALLs 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 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%) resulted Ph+ ALL and 19/245 (8%) Ph-like ALLs. Comparing the 3 groups we found that: Ph+ B-ALL 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+ B-ALLs. CD146 along with myeloid markers may help to identify a distinctive immunophenotypic pattern, useful for rapid identification in diagnostic routine of this subtype of B-ALLs that benefits from a specific therapeutic approach.

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