Table 1 Preclinical models for assessing... | American Society of Hematology

Table 1

Preclinical models for assessing multiple myeloma biology and therapies

Model	Examples	Advantages	Disadvantages
Human myeloma cell lines (HMCLs)	> 60 independent HMCL	Oncogenic diversity Genetically manipulable Well characterized Easily grown & distributed Complex screens possible Co-culture with stromal cells	Derived from advanced extramedullary MM Lacks full diversity of human MM Lack of normal microenvironment
Xenogenic transplants in immunodeficient mice	SCID NOD.SCID NOD.SCID.il2rg-	In vivo testing of HMCL therapies	Work poorly for early, intramedullary MM Tissue localization variable and aberrant Microenvironment effects unclear/aberrant Immunocompromised host
Xenogenic transplants in humanized immunodeficient mice	SCID.hu SCID.rab SCID-synth-hu	Works for HMCL & 1^o MM Manipulate microenvironment	Challenging technology Chimeric microenvironment Immunocompromised host
Syngeneic transplants of spontaneous tumors into immunocompetent mice	T2 or T33 MM tumors into C57/BL6 mice	Tumor homes to bone marrow Normal host microenvironment T33 can be grown as cell line Can genetically manipulate cells	Genetic abnormalities unclear Doesn't reflect diversity of human MM
Genetically engineered mice (de novo or transplanted tumors)	Vk*MYC tumors in MGUS prone C57/BL6 mice	Spontaneous Mimics biology of human MM De novo: early, intramedullary Transplanted: late, extramedullary Oncogenically similar to human MM	Genetic/phenotypic characterization incomplete Human MM subgroup correlation unknown Unlikely to reflect diversity of human MM

Model	Examples	Advantages	Disadvantages
Human myeloma cell lines (HMCLs)	> 60 independent HMCL	Oncogenic diversity Genetically manipulable Well characterized Easily grown & distributed Complex screens possible Co-culture with stromal cells	Derived from advanced extramedullary MM Lacks full diversity of human MM Lack of normal microenvironment
Xenogenic transplants in immunodeficient mice	SCID NOD.SCID NOD.SCID.il2rg-	In vivo testing of HMCL therapies	Work poorly for early, intramedullary MM Tissue localization variable and aberrant Microenvironment effects unclear/aberrant Immunocompromised host
Xenogenic transplants in humanized immunodeficient mice	SCID.hu SCID.rab SCID-synth-hu	Works for HMCL & 1^o MM Manipulate microenvironment	Challenging technology Chimeric microenvironment Immunocompromised host
Syngeneic transplants of spontaneous tumors into immunocompetent mice	T2 or T33 MM tumors into C57/BL6 mice	Tumor homes to bone marrow Normal host microenvironment T33 can be grown as cell line Can genetically manipulate cells	Genetic abnormalities unclear Doesn't reflect diversity of human MM
Genetically engineered mice (de novo or transplanted tumors)	Vk*MYC tumors in MGUS prone C57/BL6 mice	Spontaneous Mimics biology of human MM De novo: early, intramedullary Transplanted: late, extramedullary Oncogenically similar to human MM	Genetic/phenotypic characterization incomplete Human MM subgroup correlation unknown Unlikely to reflect diversity of human MM