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Updated: Feb 12, 2026

Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up

Flow Cytometry to Estimate Leukemia Stem Cells in Primary Acute Myeloid Leukemia and in Patient-derived-xenografts, at Diagnosis and Follow Up

Published on: March 26, 2018

CRIP1ノックダウンは急性骨髄性白血病における解糖依存性を高め、2-デオキシ-D-グルコースに対する感受性を増強する

Muhammad Asif Zeb¹, Faryal Mehwish Awan¹, Aamir Ali Khan²

¹Department of Medical Lab Technology, The University of Haripur, Haripur, 22620, Khyber Pakhtunkhwa, Pakistan.

Molecular biology reports

|February 11, 2026

要旨

Background:

Acute Myeloid Leukemia (AML) is an aggressive hematologic malignancy with suboptimal treatment outcomes, necessitating the development of novel therapeutic strategies. Metabolic reprogramming, particularly a dependency on glycolysis, is a hallmark of cancer cells. The cysteine-rich intestinal protein 1 (CRIP1) gene exhibits dual roles in cancer, but its function in AML metabolism remains unexplored. This study investigated the metabolic consequences of CRIP1 knockdown and the subsequent efficacy of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) compared to the oxidative phosphorylation (OXPHOS) inhibitor IACS-010759.

Methods:

Stable CRIP1 knockdown (CRIP1-KD) was established in the OCI-AML3 cell line using lentiviral shRNA. Metabolic changes were assessed by measuring glucose consumption and lactate secretion. Expression of lactate dehydrogenase A (LDHA) was evaluated by Western blot. The cytotoxic effects of 2-DG and IACS-010759 were determined via flow cytometry using 7-AAD staining.

Results:

CRIP1-KD cells demonstrated an 87% reduction in CRIP1 expression (*p*<0.001) and a significant increase in both glucose uptake (*p*=0.04) and lactate production (*p*=0.01) compared to scramble control (SCR) cells. This glycolytic phenotype was corroborated by a 3.3-fold upregulation in LDHA protein expression. Treatment with 2-DG resulted in a more pronounced suppression of glucose consumption and lactate production than IACS-010759 in CRIP1-KD cells (*p*=0.01). Consequently, CRIP1-KD cells exhibited significantly higher cell death after 2-DG treatment (29.10%) compared to IACS-010759 treatment (17.25%; *p*=0.003).

Conclusion:

Our findings indicate that CRIP1 knockdown induces a glycolytic switch in AML cells, rendering them exquisitely sensitive to glycolytic inhibition by 2-DG. This suggests that CRIP1 status could serve as a biomarker for predicting response to metabolic therapies and highlights 2-DG as a promising therapeutic agent for a subset of AML characterized by glycolytic dependency.

キーワード:

2-デオキシ-D-グルコース急性骨髄性白血病システインリッチ腸タンパク質1（CRIP1）白血病骨髄性酸化的リン酸化

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Intra-Peritoneal Transplantation for Generating Acute Myeloid Leukemia in Mice

Intra-Peritoneal Transplantation for Generating Acute Myeloid Leukemia in Mice

Published on: January 6, 2023

Author Spotlight: Analyzing Bone Marrow Microenvironment in Murine Hematological Malignancies

Author Spotlight: Analyzing Bone Marrow Microenvironment in Murine Hematological Malignancies

Published on: November 10, 2023

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