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THE COMMON CHRONIC LYMPHOCYTIC LEUKEMIA ANTIGEN (CCLLA)   GB FAGUET   WHAT IS THE cCLLa?  
    The common chronic lymphocytic leukemia angtigen (cCLLa) is a 69kd glycoprotein expressed on the surface of B-CLL cells (1).
  The cCLLa, a Unique Antigen among “B-CLL Markers”  
    Antigens expressed on clonal B-CLL cells are generally referred to as “B-CLL markers.” Because these antigens are differentiation antigens they are also expressed on normal B-lymphocytes (CD19, CD20, monotypic sIgs and others), or on normal T-lymphocytes (CD5). What makes the cCLLa unique among “B-CLL markers” is the fact that it is not a differentiation antigen.
  What Are the Major Differences between the cCLLa and Other “B-CLL Markers”?  
    First, not being a differentiation antigen, the cCLLa is not expressed by normal T- or B-lymphocytes whether in peripheral blood, bone marrow, or in lymphoid areas (Table 1).
 
    Second, the cCLLa is disease- and lineage-restricted. That is, it is detected on clonal cells of patients with B-CLL and related leukemias (Prolymphocytic and Hairy cell leukemias), but is not expressed by clonal cells of T-CLL or of unrelated neoplasias regardless of lineage (Table 1). Additionally, cCLLa expression in CLL, HCL and PLL of B-lineage is universal (all clonal cells of all patients) (1-3).
 
    Third, while in B-CLL the cCLLa is co-expressed with other “B-CLL markers”, its expression occasionally precedes that of other “B-CLL markers” including CD5, and is frequently detected on clonal cells that fail to express one or more such markers (3).
 
    Fourth, cCLLa expression density is cell-cycle dependent (G0/G1 to DNA phase exhibits a 100 to 1 cCLLa density ratio).   Are the differences between the cCLLa and other “B-CLL markers” clinically useful?  
    The above characteristics confer distinct advantages to using the cCLLa, both as a diagnostic and therapeutic tool. From a diagnostic standpoint, cCLLa detection facilitates distinguishing B-CLL from diseases with similar anatomic distribution or exhibiting similar cytomorphology, and provides a suitable target to probe for B-CLL cells even when diluted by large numbers of normal T- or B-lymphocytes. Examples of this are patients exhibiting emerging B-CLL clones (3) or those approaching chemotherapy-induced complete hematologic remission. From the therapeutic standpoint, cytotoxic conjugates of anti-cCLLa monoclonal antibodies shown in preclinical in vitro (4) and animal studies to exhibit potent clonal-specific cytotoxicity and suitable pharmacokinetics and biodistribution (5) offer alternative therapeutic tools for the management of refractory B-CLL.
  REFERENCES  
  1. Agee JF, Garver FA, Faguet GB. An antigen common to chronic lymphocytic and hairy cell
      leukemia cells not shared by normal lymphocytes or by other leukemic cells. Blood 1986;
      68:62-8.
  2. Faguet GB, Agee JF. Monoclonal antibodies against the chronic lymphocytic leukemia
      antigen, cCLLa: characterization and reactivity. Blood 1987; 70:437-43.
  3. Faguet GB, Agee JR, Marti GE. Clone emergence and evolution in chronic lymphocytic
      leukemia: characterization of clinical laboratory and immunophenotypic profiles of 25 patients.
      Leukemia & Lymphoma 1992; 6:345-56.
  4. Faguet GB, Agee JF. Four ricin chain A-based immunotoxins directed against the common
      chronic lymphocytic leukemia antigen. In vitro characterization. Blood 1993; 82:536-43.
  5. Faguet GB, Agee JF, DiPiro JT. Pharmacokinetics and biodistribution of two divalent,
      ricin-based anti-chronic lymphocytic leukemia immunotoxins in xenografted athymic mice.
      (Submitted for publication).
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