A CD36-dependent non-canonical lipid metabolism program promotes immune escape and resistance to hypomethylating agent therapy in AML.

Environmental lipids are essential for fueling tumor energetics, but whether these exogenous lipids transported into cancer cells facilitate immune escape remains unclear. Here, we find that CD36, a transporter for exogenous lipids, promotes acute myeloid leukemia (AML) immune evasion. We show that, separately from its established role in lipid oxidation, CD36 on AML cells senses oxidized low-density lipoprotein (OxLDL) to prime the TLR4-LYN-MYD88-nuclear factor κB (NF-κB) pathway, and exogenous palmitate transfer via CD36 further potentiates this innate immune pathway by supporting ZDHHC6-mediated MYD88 palmitoylation.

miR-29c&b2 encourage extramedullary infiltration resulting in the poor prognosis of acute myeloid leukemia.

Extramedullary infiltration (EMI), as a concomitant symptom of acute myeloid leukemia (AML), is associated with low complete remission and poor prognosis in AML. However, the mechanism of EMI remains indistinct. Clinical trials showed that increased miR-29s were associated with a poor overall survival in AML [14].

Leukemia cells remodel marrow adipocytes via TRPV4-dependent lipolysis.

Remodeling of adipocyte morphology and function plays a critical role in prostate cancer development. We previously reported that leukemia cells secrete growth differentiation factor 15 (GDF15)，which remodels the residual bone marrow (BM) adipocytes into small adipocytes and is associated with a poor prognosis in acute myeloid leukemia (AML) patients. However, little is known about how GDF15 drives BM adipocyte remodeling.

Growth differentiation factor 15 contributes to marrow adipocyte remodeling in response to the growth of leukemic cells.

Background: The adipocyte remodeling, including of the morphological change, might indicate special pathological function. Our previous study found that the morphological remodeling of larger marrow adipocytes into small marrow adipocytes correlates with a poor prognosis for acute myeloid leukemia (AML) patients. However, the mechanisms contributed to the marrow adipocyte remodeling are still poorly understood.

Consolidation Chemotherapy Prevents Relapse by Indirectly Regulating Bone Marrow Adipogenesis in Patients with Acute Myeloid Leukemia.

Background/aims: Chemotherapy is still the main strategy used to prevent the relapse of acute myeloid leukaemia (AML). As the most abundant stromal component in bone marrow (BM), marrow adipocytes have been previously shown to promote leukaemogenesis. The present study was designed to further validate whether marrow adipocytes exert synergistic effects on strengthening chemotherapeutic efficacy and evaluate the underlying mechanism.

cAMP induces cell apoptosis in multiple myeloma and overcomes bortezomib resistance.

The acquired resistance to bortezomib represents a major obstacle for multiple myeloma (MM) treatment. Studies revealed that the treatment with cyclic adenosine monophosphate (cAMP) may be a promising strategy for MM therapy. Therefore, the present study aimed to explore the mechanism of action of cAMP in MM cells.

Once-Weekly 1.6 mg/m Bortezomib BCD Regimen in Elderly Patients with Newly Diagnosed Multiple Myeloma Who are Unfit for Standard Dose Chemotherapy.

Bortezomib has shown anti-myeloma effects in combination with alkylating agents, but clinical benefits can be limited by neurotoxicity. There is less information on the efficacy and tolerability of once-weekly 1.6 mg/m bortezomib combined with cyclophosphamide and dexamethasone (BCD) regimen in elderly patients with newly diagnosed multiple myeloma who are unfit for standard dose chemotherapy.

Growth differentiation factor 15 contributes to cancer-associated fibroblasts-mediated chemo-protection of AML cells.

Background: Chemo-resistance is still a major obstacle in efforts to overcome acute myeloid leukemia (AML). An emerging concept has proposed that interactions between the bone marrow (BM) microenvironment and leukemia cells reduce the sensitivity of the leukemia cells to chemotherapy. As an important element of the tumor microenvironment, the cancer-associated fibroblasts (CAFs) are considered to be activated modulators in the chemo-resistance of many solid tumors.

Effective identification and localization of immature precursors in bone marrow biopsy.

Abnormal localization of immature precursors (ALIP) aggregating and clustering in bone marrow biopsy appears earlier than that of bone marrow smears in detection of the relapse of acute myelocytic leukemia (AML). But traditional manual ALIP recognition has many shortcomings such as prone to false alarms, neglect of distribution law before three immature precursor cells gathered, and qualitative analysis instead of quantitative one. So, it is very important to develop a novel automatic method to identify and localize immature precursor cells for computer-aided diagnosis, to disclose their patterns before ALIP with the development of AML.

Leukemia propagating cells rebuild an evolving niche in response to therapy.

Residence of cancer-propagating cells (CPCs) within preferential microenvironmental niches has a major part in evading therapy. However, the nature of niches involved and the mechanisms protecting CPCs remain largely unknown. We addressed these issues in mouse transplantation models of acute lymphoblastic leukemia (ALL).

[Correlation between ALIP-like cluster and fibrous proliferation in bone marrow of patients with acute myeloid leukemia in CR phase].

This study was purposed to elucidate the prognostic values of ALIP (abnormal location of immature precursors)-like clusters and fibrous proliferation in bone marrow of AML patients in CR phase and the correlation between them. The bone marrow biopsy sections from 47 AML patients during admitting to relapse or till lost follow-up were examined retrospectively. The 47 patients were divided into pre-relapsed group and non-relapsed group according to relapse or not at end of follow-up.

Clustered precursors in bone marrow sections predict early relapse in patients with acute myeloid leukemia within hematologic remission.

Background: Bone marrow (BM) aspiration is largely used for relapse assessment in acute myeloid leukemia (AML). It remains unclear what roles that BM trephine biopsy plays on relapse assessment.

Methods: Bone marrow (BM) sections during complete remission (CR) from 60 acute myeloid leukemia (AML) patients were retrospectively analyzed.

Clustered immature myeloid precursors in intertrabecular region during remission evolve from leukemia stem cell near endosteum and contribute to disease relapse in acute myeloid leukemia.

Most acute myeloid leukemia (AML) cannot be cured because leukemia stem cells (LSC) will contribute to eventual relapse. However, how LSC initiate relapse is not yet fully understood. We performed a retrospective study on bone marrow sections from AML patients during complete remission (CR), demonstrating that single and double immature myeloid precursors were located near endosteum and clustered precursors (≥ 3 cells/group) in intertrabecular region.

[Influence of pre-ALIP number and its distance from trabeculae on AML relapse].

This study was purposed to detect the abnormal quantity and localization of pre-ALIP in bone marrow of acute myelocytic leukemia patients (AML) during the complete remission (CR) and investigate their correlation with AML relapse. The bone marrow biopsy and prognosis of 62 patients with CR were retrospectively analyzed. The bone marrow was divided into the pre-relapse group and the no-relapse group according to prognosis of patients.

[Characteristics of "pre-ALIP" in bone marrow sections of patients with acute myeloid leukemia].

To detect the characteristics of "pre-ALIP" and to investigate their relevance with the development of acute myeloid leukemia (AML) by computer image procession technology, bone marrow (BM) was collected by aspiration/trephine biopsy from AML patients during the complete remission (CR). BM sections were stained by HGF (haematoxylin-Giemsa-acid fuchsin) and photographed by optical microscope imaging system. 4 kinds of computer image segmentation technologies were compared to select the best one for detecting the localization and quantitation of the precursor cells.

[Earlier hematopoietic reconstitution by mouse cord blood transplantation combined with bone marrow c-kit(+) hematopoietic progenitor cells].

This study was purposed to investigate the accelerating effect of newborn mouse cord blood transplantation combined with hematopoietic progenitor cells of bone marrow (BM) on the early hematopoietic reconstitution after transplantation, and the long-term chimerism of cord blood-derived cells, so as to develop a combined transplantation method for accelerating the early hematopoietic reconstitution. The lin(-)sca-1(-)c-kit(+) (c-kit(+)) cells and lin(-)sca-1(+) (sca-1(+)) cells in the bone marrow of BDF1 mice were isolated by MACS method. Biological characteristics in vitro of isolated fractions were observed and compared by semisolid colony culture combined with Giemsa staining.