Growth factor receptor profile of CD34⁺ cells in AML and B‐lineage ALL and in their normal bone marrow counterparts

Abstract

Leukaemic cells show a low clonogenic activity and a heterogeneous proliferative response to growth factors. We investigated whether this could be due to an altered expression of growth factor receptors on the leukaemic precursors. Receptors for G-CSF, stem cell factor (SCF), IL-3, IL-6 and IL-7 were detected on CD34+ cells in AML and B-lineage ALL with monoclonal antibodies and flow cytometry. The expression was compared with that on myeloid and B-lymphoid CD34+ cells in normal bone marrow. Leukaemic CD34+ cells expressed the same receptors as their normal counterparts. AML and B-lineage ALL could be distinguished by the growth factor receptor profile of their CD34+ cells. SCFR, G-CSFR and IL-6Ralpha were found in AML, IL-7R in B-lineage ALL and IL-3Ralpha in both. IL-3Ralpha was upregulated in AML and B-lineage ALL CD34+ cells, while samples with low or high expression were present for the other receptors. This variable expression could correlate with the heterogeneous response of leukaemic cells to growth factors. Functional studies on isolated CD34+ cells are needed to investigate this further.

PU.1 Opposes IL-7–Dependent Proliferation of Developing B Cells with Involvement of the Direct Target Gene Bruton Tyrosine Kinase

“…Btk and Blnk were found to be targets of PU.1 and Spi-B in our studies, and they are established as tumor suppressors in human precursor B-ALL (36,42). Expression of the IL-7R has long been known to be a common feature of human childhood or adult B cell leukemia (43,44). Finally, although IL-7 has been previously suggested to be not required for human B cell development, gain-of-function mutations in the human IL7R gene are associated with precursor B-ALL (45,46).…”

Targeting of acute myeloid leukemia in vitro and in vivo with an anti-CD123 mAb engineered for optimal ADCC

“…[5][6][7] CD123 (interleukin (IL)-3-Ra) is expressed in a variety of hematological malignancies including AML, myelodysplastic syndrome, B-cell acute lymphoblastic leukemia, Hodgkin's lymphoma, hairy cell leukemia, systemic mastocytosis, plasmacytoid dendritic cell (pDC) leukemia and chronic myeloid leukemia. [8][9][10][11][12] The majority of AML blasts express CD123 and it is also overexpressed on CD34 þ CD38 À LSCs compared with normal hematopoietic stem cells 13 and other normal tissues. This difference provides an opportunity to target the malignant cells selectively, and a CD123-specific antibody-based therapy could provide an attractive option for AML treatment, offering specificity and low toxicity compared with conventional chemotherapeutics.…”

Classification of Acute Leukemia

“…ALL of B or T lineage can additionally express myeloid antigens or stem-cell antigen CD34. The latter has little diagnostic relevance but can be prognostically important (De Waele 2001) The scoring system recently proposed by the EGIL group addressed the characterization of the acute leukemia as B or T lineage ALL, or AML by including the most specific markers for the lymphoid and myeloid lineages among those of earlier stages of cell differentiation, plus some non-specific but stem-cell markers. The system introduced a modified terminology specific to each 'maturation' step within the B-or T-cell lineage (EGIL 1995) and was confirmed as adequate for both diagnosis and subclassification of ALL (Thalhammer-Scherrer 2002).…”