In the present study, its aimed to compare the amount of CD45+/CD34+/CD38−/CD26+ levels of
CML stem cells in CML patients with and without BCR-ABL hematopoiesis. Therefore, the amount
of CD45+/CD34+/CD38−/CD26+ levels of CML stem cells in CML patients will be analyzed using
bone marrow and peripheral blood samples and whether leukemic stem cells are present in the
bone marrow and at what amount, if present, although these cells are cleared from the
peripheral blood, will be investigated. Additionally this study would pave the way for
further cellular treatment strategies against CML stem cells, being the pioneer of
development of curative treatments in CML. Until now, TKI discontinuation studies have failed
in patients with long-term BCR-ABL negativity. There is a chance for cure in patients in whom
the BCR-ABL status becomes negative with chimeric antigen receptor (CAR) T-cell treatment
modalities which target leukemic stem cells. Also, monoclonal antibodies and/or cellular
treatments targeting leukemic stem cells are the main treatment strategy is to reduce the CML
treatment-related cost. In the international platform, the accurate definition of leukemic
stem cell in CML and development of targeted cellular treatments have been also paid a great
attention with a given priority for patent application. The primary objective of the present
study is to accurately detect leukemic stem cells in CML and to estimate the threshold value
for the prediction of recurrence or cure.
To the best of investigators knowledge, there is a very limited number of studies in the
literature and there is no study available comparing leukemic stem cells
(CD45+/CD34+/CD38-/CD26+) in patients with BCR-ABL-positive hematopoiesis and CML patients
with BCR-ABL activity inhibition under TKI therapy in Turkey. Therefore,for the first time,
it is planned to evaluate the prognostic value of the amount of leukemic stem cells in CML
and to tailor individual treatment options.
Newly diagnosed CML patients or patients with a previous diagnosis under follow-up with or
without TKIs will be included in this study. The patients will be divided into two groups as
follows:
Group 1: Patients with BCR-ABL-positive hematopoiesis (newly diagnosed CML patients, CML
patients with leukocytosis, CML patients without a hematological and/or cytogenetic and/or
molecular response, CML patients whose BCR-ABL status becomes negative and then positive)
will be included.
Group 2: Patients with CML with BCR-ABL activity inhibition under TKI therapy (patients with
major molecular response (MMR) and/or deeper response) will be included.
Peripheral blood samples from 30 patients and bone marrow aspiration samples from 20 patients
will be collected for each group. A total of 100 patients will be included in the study. The
number of bone marrow aspiration samples is limited to 20 patients for each group, as this
method is more invasive with a higher rate of complications. Peripheral blood samples will be
collected simultaneously in patients in whom bone marrow samples are collected. For an
accurate examination, the bone marrow samples and the peripheral blood samples will be
concomitantly analyzed for each individual patient. The presence and amount of
CD45+/CD34+/CD38-/CD26+ leukemic stem cells will be analyzed using multicolor flow cytometry
at Ankara University, Faculty of Medicine, Ibni Sina Hospital, Hematology Lab. The peripheral
blood and bone marrow samples obtained at Hacettepe University and Ege University will be
transferred to Ankara University, Faculty of Medicine, Ibni Sina Hospital, Hematology Lab in
accordance with the codes of the Biological Material Transfer Agreement. As bone marrow
aspiration and BCR-ABL molecular testing are routinely used in the diagnosis and follow-up of
CML patients, these interventions pose no additional burden for the patients.