THE BONE-MARROW OF MULTIPLE-MYELOMA PATIENTS CONTAINS B-CELL POPULATIONS AT DIFFERENT STAGES OF DIFFERENTIATION THAT ARE CLONALLY RELATED TO THE MALIGNANT PLASMA-CELL
D. Billadeau et al., THE BONE-MARROW OF MULTIPLE-MYELOMA PATIENTS CONTAINS B-CELL POPULATIONS AT DIFFERENT STAGES OF DIFFERENTIATION THAT ARE CLONALLY RELATED TO THE MALIGNANT PLASMA-CELL, The Journal of experimental medicine, 178(3), 1993, pp. 1023-1031
One of the distinguishing features of multiple myeloma (MM) is the pro
liferation of a clonal plasma cell population in the bone marrow (BM).
It is of particular interest that the tumor plasma cells appear to be
restricted to the microenvironment of the BM and are rarely detected
in the peripheral system, yet the disease is found widely disseminated
throughout the axial skeleton. Furthermore, isolation of MM tumor cel
l lines has proven to be quite problematic due to their slow growth ra
te. These observations have instigated the search for earlier cells in
the B cell lineage that are clonally related to the plasma cell tumor
and that may represent the growth fraction of the tumor. We used alle
le-specific oligonucleotides (ASO) derived from the third complementar
ity determining region of the rearranged tumor immunoglobulin heavy ch
ain gene to detect isotypes clonally related to the plasma cell tumor.
By reverse transcribing RNA from the BM with a panel of CH primers (m
u, delta, alpha, and gamma), followed by ASO-polymerase chain reaction
amplification, we demonstrate the existence of preswitch isotype spec
ies that are clonally related to the myeloma tumor. Furthermore, we sh
ow that separation of the BM cells into CD45+ and CD38+ cell populatio
ns results in a lineage-specific expression of the clonally related RN
A molecules, with the Cmu and Cdelta in the CD45+, and Cgamma in the C
D38+ population. Interestingly, clonally related Calpha transcripts ar
e also derived from the CD45+ fraction. These results confirm the pres
ence of B cell populations clonally related to the plasma cell tumor a
nd are consistent with models that propose the existence of myeloma pr
ecursors.