title: Polymorphism of CD44 influences the efficacy of CD34(+) cells mobilization in patients with hematological malignancies.
abstract: In the last decade, peripheral blood was the main source of hematopoietic stem cells (HSC) for autologous and allogeneic transplantation. The exact mechanisms of HSC mobilization are still not clear and the efficacy of the procedure is hardly predictable. Ligand-receptor interactions of adhesion molecules, such as SDF1/CXCR4, VLA4/VCAM-1, or CD44/osteopontin, play an important role in homing of HSC in the hematopoietic niche. There is some evidence that disruption of the ligand-receptor complex leads to the egress of HSCs to the peripheral blood. The aim of the present study was the evaluation of constitutive polymorphism of genes encoding cytokines and receptors present in the HSC niche and their impact on the efficacy of mobilization of HSCs in patients with hematological malignancies. We enrolled 110 patients (60 females and 50 males) in the study. The median age of the patients was 55 (range, 22 to 69) years. The group consisted of patients with multiple myeloma (n = 74), non-Hodgkin lymphoma (n = 19), Hodgkin lymphoma (n = 15), or acute myeloid leukemia (n = 2). The mobilization procedures comprised chemotherapy and subsequent granulocyte-colony stimulating factor (G-CSF) at a dose of 10 μg/kg daily. The poor mobilizers group was defined according to Italian National Bone Marrow Transplant Registry criteria: patients with peak CD34(+) in the peripheral blood < 20/μL or total yield < 2 × 10(6) CD34(+) cells/kg body weight in maximum 3 aphereses. Genotyping was performed using standard PCR-based assays. The group of patients (N = 108) who achieved minimal threshold for collections (CD34(+) at least 10/μL) proceeded to apheresis. The median total yield of CD34(+) in this group was 5.6 × 10(6) cells/kg body weight, whereas the median number of cells collected during the first apheresis was 3.3 × 10(6) cells/kg body weight. Median number of days of G-CSF treatment before first apheresis was 10. Fifteen patients fulfilled the criteria for poor mobilizer. The group of poor mobilizers had higher frequency of TT genotype in rs13347 (CD44) gene (CC+ CT versus TT P = .047). Patients homozygous for T allele had a lower total yield of CD34(+) cells/kg body weight than the group with allele C (median, 3.7 × 10(6)/kg versus 5.8 × 10(6)/kg; P = .019) and a lower number of CD34(+) cells gathered during first apheresis (.95 × 10(6)/kg versus 3.3 × 10(6)/kg, P = .04). Multivariate logistic regression analysis revealed that the CD44 TT genotype was the only factor associated with 5-fold higher risk of poor mobilization (P = .037). Polymorphic variants of CXCR4 and VCAM-1 did not significantly influence the efficacy of HSCs mobilization in our group of patients. In conclusion, our results indicate that among investigated single nucleotide polymorphisms (SNPs), only CD44 rs13347 has an impact on the efficacy of HSCs mobilization in patients with hematologic malignancies. CD44 SNPs analysis may be helpful for predicting the poor mobilizers population who may benefit from newer modalities using adhesion molecules inhibitors.
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland. Electronic address: aszmigielska@poczta.onet.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Szmigielska-Kaplon
authors.affiliation: Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.affiliation: Department of Medical Biochemistry, Medical University of Lodz, Lodz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Hamara
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Robak
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wolska
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Pluta
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Czemerska
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Krawczynska
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Jamroziak
authors.affiliation: Department of Sports Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Szmigielska
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.affiliation: Department of Hematology, Medical University of Lodz, Lodz, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wierzbowska
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000096:biosynthesis* / Q000097:blood; D001781:Blood Component Removal / Q000379:methods; D005260:Female; D005838:Genotype; D019337:Hematologic Neoplasms / Q000097:blood / Q000235:genetics*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019718:Receptors, CXCR4 / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; C497483:CD44 protein, human; C527276:CXCR4 protein, human; D018960:Hyaluronan Receptors; D019718:Receptors, CXCR4; D019010:Vascular Cell Adhesion Molecule-1
keywords: CD44; Mobilization of hematopoietic stem cells; Single nucleotide polymorphism