Mesenchymal stem cells from patients with chronic myeloid leukemia do not express BCR-ABL and have absence of chimerism after allogeneic bone marrow transplant.

نویسندگان

  • R C V Carrara
  • M D Orellana
  • A M Fontes
  • P V B Palma
  • S Kashima
  • M R Mendes
  • M A Coutinho
  • J C Voltarelli
  • D T Covas
چکیده

Bone marrow is a heterogeneous cell population which includes hematopoietic and mesenchymal progenitor cells. Dysregulated hematopoiesis occurs in chronic myelogenous leukemia (CML), being caused at least in part by abnormalities in the hematopoietic progenitors. However, the role of mesenchymal stem cells (MSCs) in CML has not been well characterized. The objectives of the present study were to observe the biological characteristics of MSCs from CML patients and to determine if MSCs originate in part from donors in CML patients after bone marrow transplantation (BMT). We analyzed MSCs from 5 untreated patients and from 3 CML patients after sex-mismatched allogeneic BMT. Flow cytometry analysis revealed the typical MSC phenotype and in vitro assays showed ability to differentiate into adipocytes and osteoblasts. Moreover, although some RT-PCR data were contradictory, combined fluorescence in situ hybridization analysis showed that MSCs from CML patients do not express the bcr-abl gene. Regarding MSCs of donor origin, although it is possible to detect Y target sequence by nested PCR, the low frequency (0.14 and 0.34%) of XY cells in 2 MSC CML patients by fluorescence in situ hybridization analysis suggests the presence of contaminant hematopoietic cells and the absence of host-derived MSCs in CML patients. Therefore, we conclude that MSCs from CML patients express the typical MSC phenotype, can differentiate into osteogenic and adipogenic lineages and do not express the bcr-abl gene. MSCs cannot be found in recipients 12 to 20 months after BMT. The influence of MSCs on the dysregulation of hematopoiesis in CML patients deserves further investigation.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Detection of BCR/ABL Translocation in Bone Marrow Derived Mesenchymal Stem Cells in Egyptian CML Patients

BACKGROUND Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of hematopoietic stem cells. It is characterized at the cytogenetic level by Philadelphia (ph) chromosome and at the molecular level by the BCR/ABL gene rearrangement. Bone marrow derived mesenchymal stem cells (MSCs) are pluripotent stem cells that can differentiate into several mesenchymal tissues. AIM To obse...

متن کامل

Early assessment of donor CD34+ positive cells chimerism after allogeneic stem cell transplantation in acute myeloid leukemia/myelodysplastic syndrome patients – pilot study

Introduction. In high-risk acute myeloid leukaemia/myelodysplastic syndrome patients, relapse remains the major cause of treatment failure after allogeneic stem cell transplantation (alloSCT). The investigation of lineage-specific chimerism has become an important tool in the management of patients during the post-transplant period. Aim. Early assessment of lineage specific chimerism in patient...

متن کامل

Adoptive immunotherapy of BCR-ABL-induced chronic myeloid leukemia-like myeloproliferative disease in a murine model.

Donor leukocyte infusion (DLI) can induce graft-versus-leukemia (GvL) reactions in patients with chronic myeloid leukemia (CML) relapsing after allogeneic bone marrow transplantation (BMT), but the mechanisms of the antileukemic effect of DLI are unknown, and the procedure is complicated by graft-versus-host disease (GvHD) and graft failure. Here, we adapted a murine retroviral BMT model of Phi...

متن کامل

Kinetics of the graft-versus-leukemia response after donor leukocyte infusions for relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation.

Little is known about the mechanisms and the kinetics of the so-called graft-versus-leukemia (GVL) response induced by donor lymphocyte infusions (DLI) in patients with leukemic relapse after allogeneic bone marrow transplantation (BMT). We sought to elucidate this problem by sequentially studying three patients with relapsed chronic myeloid leukemia after sex-mismatched BMT from time before do...

متن کامل

Persistence of myeloid progenitor cells expressing BCR-ABL mRNA after allogeneic bone marrow transplantation for chronic myelogenous leukemia.

Previous studies have shown that tumor-specific bcr-abl mRNA can often be detected by polymerase chain reaction. (PCR) for months to years after allogeneic bone marrow transplantation (BMT) for chronic myelocytic leukemia (CML). Nevertheless, the presence of bcr-abl mRNA by itself does not invariably predict for clinical relapse post-BMT. This has led to the hypothesis that bcr-abl mRNA might b...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas

دوره 40 1  شماره 

صفحات  -

تاریخ انتشار 2007