For patients with chronic myeloid leukemia Mission We aim to create a society in which imaging technology can bring light to every patient’s future and enable them to face the challenges of their treatment with peace of mind. 1.We can see how well each individual leukemia cell responds to each drug. 2.We can diagnose whether a drug will be effective before it is administered. (We can also determine efficacy during treatment) 3.In the future, this technology may help us understand whether to stop medication.
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Pre-treatment diagnostics of TKI for CML therapeutics utilizing fluorescence bioimaging technology (Förster Resonance Energy Transfer: FRET)

CML, chronic myelogenous leukemia, is a blood cancer that develops when the causative protein BCR::ABL appears in cells. TKIs, molecular targeted drugs that suppress the tyrosine kinase activity of BCR::ABL, have been used for treatment of CML. However, the problem is that a successful drug response is not known until treatment is actually started and follow-up is conducted. We have developed "opto-diagnostics" to detect the activity of BCR::ABL, utilizing the principle of Förster resonance energy transfer (FRET), with the substrate CrkL of BCR-ABL. This makes it possible to analyze the drug sensitivity of CML cells collected from patients at the single-cell level, prior to the start of treatment.

Förster Resonance Energy Transfer (FRET) Principle and Pickless

Fluorescence:Light of a specific wavelength is emitted by excitation light of a specific wavelength.
FRET:Fluorescence properties are changed by energy transfer when other fluorescent molecules are present in the vicinity, i.e., a phenomenon of color change.
i.e., a phenomenon of color change. blue yellow
Opto-diagnostics “Pickles” Pickles:Phosphorylation indicator of CrkL en substrate
Unphosphorylated form = TKI is effective → Blue, Phosphorylated form = TKI is ineffective → Yellow blue yellow

Procedure for determining drug efficacy

Day 0

0.bone marrow sampling

Day 1

1.Isolation of CML cells by density gradient centrifugation

2.Introduction of Opto-diagnostics “Pickles” into the CML cells by electroporation

Day 2

3.TKI treatment

4.Imaging

Day 3

5.Image analysis

6. Determination of drug efficacy

Ineffective Effective

Preliminary Clinical Performance Tests

1.Typical samples from incipient patients
2
“Quick Responders” (patients who can achieve treatment-free remission): approx. 50%）12,000 patients × 0.5 × ¥2.5m/year= Medical cost reduction approx. ¥15 B/y in Japan.

Fluorescence bioimaging technology enables highly sensitive and
quantitative measurement of protein movement and
function in living cells.
Our goal is to apply this technology to clinical testing.