Bone Lesions in Molecular Subtypes of Multiple Myeloma
http://www.100md.com
《新英格兰医药杂志》
To the Editor: In a recent article in the Journal, Tian et al. showed the power of microarray data mining in finding new links between single genes (e.g., dickkopf1 [DKK1]) and clinical features of a disease (in the case of DKK1, bone lesions in multiple myeloma).1 We recently divided multiple myeloma into five molecular subtypes (called translocation and cyclin D [TC] types) on the basis of cyclin D1 messenger RNA expression (without an 11q13 translocation) and the presence of translocations in the immunoglobulin heavy-chain gene, from chromosome 14 to 11q13 or 6p21, to 4p16, and to 16q23 or 20q11.2,3,4 Correlations between molecular subtypes and prognosis have recently been identified, including a good prognosis with t(11;14) and a poor prognosis with t(4;14) and t(14;16).5
We took the microarray data set described by Tian et al.1 and correlated the presence of bone lesions on magnetic resonance imaging (MRI) with this molecular classification. We found a very close correlation (Table 1), with about 90 percent of the patients in groups TC1 and TC2 having bone disease, as compared with just over half the patients in groups TC4 and TC5. Within each group (with the possible exception of TC5), the patients with bone disease tended to have higher levels of DKK1 than patients without bone disease. However, among the patients with bone disease, the levels of DKK1 were significantly higher in the TC1 and TC2 groups than in the other three groups (P=0.007). This finding suggests that there are fundamental differences among distinct molecular subtypes of myeloma with respect to the biology underlying bone disease. One important clinical correlate would be earlier consideration of the use of prophylactic bisphosphonates in the TC1 and TC2 groups, which have a high incidence of bone disease.
Table 1. Relation of Molecular Subtypes of Multiple Myeloma to the Presence or Absence of Bone Lesions on MRI.
These findings identify differences in the incidence of bone disease according to distinct myeloma subtypes and thus provide support for this molecular classification. We propose that molecular subtypes of myeloma be considered separate diseases with different biologic and clinical features, prognoses, and responses to therapy.
Davide F. Robbiani, M.D.
Marta Chesi, Ph.D.
P. Leif Bergsagel, M.D.
Weill Medical College of Cornell University
New York, NY 10021
References
Tian E, Zhan F, Walker R, et al. The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 2003;349:2483-2494.
Kuehl WM, Bergsagel PL. Multiple myeloma: evolving genetic events and host interactions. Nat Rev Cancer 2002;2:175-187.
Bergsagel PL, Kuehl WM. Critical roles for immunoglobulin translocations and cyclin D dysregulation in multiple myeloma. Immunol Rev 2003;194:96-104.
Barille-Nion S, Barlogie B, Bataille R, et al. Advances in biology and therapy of multiple myeloma. Hematology (Am Soc Hematol Educ Program) 2003:248-78.
Moreau P, Facon T, Leleu X, et al. Recurrent 14q32 translocations determine the prognosis of multiple myeloma, especially in patients receiving intensive chemotherapy. Blood 2002;100:1579-1583.
We took the microarray data set described by Tian et al.1 and correlated the presence of bone lesions on magnetic resonance imaging (MRI) with this molecular classification. We found a very close correlation (Table 1), with about 90 percent of the patients in groups TC1 and TC2 having bone disease, as compared with just over half the patients in groups TC4 and TC5. Within each group (with the possible exception of TC5), the patients with bone disease tended to have higher levels of DKK1 than patients without bone disease. However, among the patients with bone disease, the levels of DKK1 were significantly higher in the TC1 and TC2 groups than in the other three groups (P=0.007). This finding suggests that there are fundamental differences among distinct molecular subtypes of myeloma with respect to the biology underlying bone disease. One important clinical correlate would be earlier consideration of the use of prophylactic bisphosphonates in the TC1 and TC2 groups, which have a high incidence of bone disease.
Table 1. Relation of Molecular Subtypes of Multiple Myeloma to the Presence or Absence of Bone Lesions on MRI.
These findings identify differences in the incidence of bone disease according to distinct myeloma subtypes and thus provide support for this molecular classification. We propose that molecular subtypes of myeloma be considered separate diseases with different biologic and clinical features, prognoses, and responses to therapy.
Davide F. Robbiani, M.D.
Marta Chesi, Ph.D.
P. Leif Bergsagel, M.D.
Weill Medical College of Cornell University
New York, NY 10021
References
Tian E, Zhan F, Walker R, et al. The role of the Wnt-signaling antagonist DKK1 in the development of osteolytic lesions in multiple myeloma. N Engl J Med 2003;349:2483-2494.
Kuehl WM, Bergsagel PL. Multiple myeloma: evolving genetic events and host interactions. Nat Rev Cancer 2002;2:175-187.
Bergsagel PL, Kuehl WM. Critical roles for immunoglobulin translocations and cyclin D dysregulation in multiple myeloma. Immunol Rev 2003;194:96-104.
Barille-Nion S, Barlogie B, Bataille R, et al. Advances in biology and therapy of multiple myeloma. Hematology (Am Soc Hematol Educ Program) 2003:248-78.
Moreau P, Facon T, Leleu X, et al. Recurrent 14q32 translocations determine the prognosis of multiple myeloma, especially in patients receiving intensive chemotherapy. Blood 2002;100:1579-1583.