The Reliability and Specificity of c-kit for the Diagnosis of Acute Myeloid Leukemias and Undifferentiated Leukemias

Abstract

We document findings on c-kit (CD117) expression in 1,937 pediatric and adult de novo acute leukemia cases, diagnosed in five single European centers. All cases were well characterized as to the morphologic, cytochemical, and immunologic features, according to the European Group for the Immunological Classification of Leukemias (EGIL). The cases included 1,103 acute myeloid leukemia (AML), 819 acute lymphoblastic leukemia (ALL), 11 biphenotypic acute leukemia (BAL), and 4 undifferentiated (AUL). c-kit was expressed in 741 (67%) AML cases, regardless of the French-American-British (FAB) subtype, one third of BAL, all four AUL, but only in 34 (4%) of ALL cases. The minority of c-kit+ ALL cases were classified as: T-cell lineage (two thirds), mainly pro-T–ALL or T-I, and B lineage (one third); cells from 62% of these ALL cases coexpressed other myeloid markers (CD13, CD33, or both). There were no differences in the frequency of c-kit+ AML or ALL cases according to age being similar in the adult and pediatric groups. Our findings demonstrate that c-kit is a reliable and specific marker to detect leukemia cells committed to the myeloid lineage, and therefore should be included in a routine basis for the diagnosis of acute leukemias to demonstrate myeloid commitment of the blasts. c-kit expression should score higher, at least one point, in the system currently applied to the diagnosis of BAL, as its myeloid specificity is greater than CD13 and CD33. Findings in ALL and AUL suggest that c-kit identifies a subgroup of cases, which may correspond to leukemias either arising from early prothymocytes and/or early hematopoietic cells, both able to differentiate to the lymphoid and myeloid pathways.

Adult T‐biphenotypic acute leukaemia: clinical and biological features and outcome

“…These mixed-lineage leukaemias probably included both true BAL and other forms of AL with aberrant expression of one or two markers of another lineage. The BAL scoring system forwarded by EGIL (Bene et al, 1995;Bene et al, 1998) is based on the number and specificity of the myeloid and lymphoid antigens expressed simultaneously on leukaemic cells. Although several antigens are considered lineage-specific (such as CD3 and TCR on T-lymphoid cells, and MPO on myeloid cells), other markers are not restricted to a specific lineage; for example, CD2 and CD7 have been found on myeloid blasts (Buccheri et al, 1993).…”

Expression of AC133 and CD117 on candidate normal stem cell populations in childhood B‐cell precursor acute lymphoblastic leukaemia

“…CD117, the receptor for stem cell factor, is expressed on immature normal and leukaemic myeloid cell but only rarely on leukaemic blasts in B-cell precursor ALL (Bene et al, 1998;Sperling et al, 1997). Thus, CD117 was thought a be another good candidate to separate normal from leukaemic cells.…”

“…In all six patients (UPN 1,7,9,18,20 and 26) an AC133-positive CD19 À CD34 progenitor/stem cell population could be detected, whereas the CD19 CD34 /leukaemic cell clone was AC133-negative (Fig 2). Expression of CD117 within the CD19 À CD34 cell compartment Due to the rarity of CD117 expression in B-cell precursor ALL (Bene et al, 1998;Sperling et al, 1997), CD117 was thought to be a good marker to distinguish between residual normal and leukaemic cells. Analysis of CD117 expression on CD45negative B-cell precursor ALL has shown that the CD19 À CD34 CD45 candidate normal progenitor/stem cells expressed CD117 (patient UPN 11, Fig 1; UPN 12, Fig 3; UPN 25; UPN 28).…”

Leukemic cells and the cytokine patchwork

“…Specific receptors are absolute requirements for cytokine action to occur. However, many growth factor receptors are manifested in a low density both on normal and leukemic progenitors and receptor expression may not be detected in a resting metabolic or proliferative state [58][59][60][61][62][63]. If only a small fraction of blast cells are clonogenic and the number of specific cytokine binding sites is low, most assays may not be sensitive enough to detect receptor expression at the protein level, unless a significant portion of non-clonogenic cells express the same receptor [64,65].…”