big win

Rice and MD Anderson researchers discover exciting new leukemia treatment

Rice biochemist Natasha Kirienko and MD Anderson physician-scientist Marina Konopleva made the striking discovery. Photo by Jeff Fitlow

Rice University and MD Anderson researchers have just discovered a potential one-two punch that could, they hope, knock out an insidious disease.

A recent study in the journal Leukemia centers on potential new drugs that, with the help of other medications, can thwart leukemia cells.

Specifically, Rice biochemist Natasha Kirienko and MD Anderson physician-scientist Marina Konopleva screened some 45,000 small-molecule compounds to find a few that targeted mitochondria, according to Rice press materials.

In this innovative new study, the team selected eight of the most promising compounds, identified between five and 30 closely related analogs for each, and conducted tens of thousands of tests to systematically determine how toxic each analog was to leukemia cells. This was measured both when administered individually or in combination with existing chemotherapy drugs like doxorubicin, notes a release.

Previously, Kirienko’s lab had shown the eight compounds targeted energy-producing machinery inside cells called mitochondria. Mitochondria, which work nonstop in every living cell, wear out with use. The chosen eight compounds induce mitophagy, which can be described as how cells decommission and recycle deficient and used-up.

Notably, during times of extreme stress, cells can temporarily forgo mitophagy for an emergency energy boost. Previous research has shown leukemia cells have far more damaged mitochondria than healthy cells and are also more sensitive to mitochondrial damage than healthy cells.

Thus, Kirienko and Konopleva reasoned that mitophagy-inducing drugs might weaken leukemia cells and make them more susceptible to chemotherapy. Synergy — using two or more drugs in treatment — is key.

“The point of synergy is that there are concentrations, or dosages, where a single drug doesn't kill,” Kirienko said. “There is no death of healthy cells or cancer cells. But administering those same concentrations in combination can kill a considerable amount of cancer cells and still not affect healthy cells.”

The team tested the toxicity of its mitophagy-inducing compounds and combinations against acute myeloid leukemia (AML) cells, the most commonly diagnosed form of the disease. They then tested the six most effective AML-killing compounds against other forms of leukemia, finding that five were also effective at killing acute lymphoblastic leukemia (ALL) cells and chronic myelogenous leukemia (CML) cells.

Studies found all the mitophagy-inducing drugs caused far less harm to healthy cells.

Finally, the researchers tested one of the most effective mitochondria-targeting compounds, PS127E, using a cutting-edge technique called a patient-derived xenograft (PDX) model. Also referred to as a “mouse clinical trial,” mice are implanted with cancer cells from a leukemia patient. As the cells grow, the mouse is exposed to a drug or combination of drugs as a closer-than-cells test of the treatment’s effect.

Importantly, PDX tests on one compound, PS127E, showed it was effective at killing AML cells in mice, Rice notes, signaling promising news.

“Although this is very promising, we’re still some distance from having a new treatment we can use in the clinic,” Kirienko added. “We still have a lot to discover. For example, we need to better understand how the drugs work in cells. We need to refine the dose we think would be best, and perhaps most importantly, we need to test on a wide variety of AML cancers. AML has a lot of variations, and we need to know which patients are most likely to benefit from this treatment and which are not. Only after we’ve done that work, which may take a few years, would we be able to start testing in humans.”

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This article originally ran on CultureMap.

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Building Houston

 
 

With the consumer price index rising 9.1 percent since last year, many Americans are evaluating new employment opportunities with better pay. However, employees would be wise to consider the risks of accepting a new position in the face of inflation and a possible recession, which could leave employers unable to sustain higher wages and generous benefits.

As a safer option in the longterm, employees may wish to ask for a raise from their current management, yet many do not know how to start the conversation. By understanding best practices for negotiations, employees can improve their chances of obtaining a pay raise without undermining relationships.

Understand the risks of job-hopping

Conventional wisdom suggests that job hopping can result in higher salary increases than an annual raise. During the pandemic, many employees took advantage of labor market shortages to secure new positions for higher pay. However, job hopping presents risks, particularly in an uncertain economic environment. Companies may institute “last in, first out” layoffs, leaving recent hires unemployed.

Even in strong economic conditions, job-hoppers face uncertain outcomes. When employees leave a company, they may leave behind teammates, mentors, client partnerships and friendships years in the making. These relationships can redevelop in a new organization, but employees may find themselves in an unfamiliar setting, facing unrealistic expectations or unexpected challenges that were not clear during the interview process.

Prepare ahead of time

Before approaching management with a request for a raise, employees should understand their own financial needs and how much additional compensation would improve their finances. If inflation has caused financial strain, employees should gather recent data on inflation, including the consumer price index, to share with management. The more information employees can offer about changing economic conditions, the more management will understand and accept their position.

Focus on the positive

Employees should begin a conversation about salary with praise for the organization and a reiteration of their commitment to the team. By beginning on a positive note, employees set the tone for a mutually productive conversation. Although employees may view salary negotiations as adversarial across the table, productive negotiations are a conversation with both employee and employer on the same team.

Likewise, while employees may worry about looking greedy, employees should not let that fear prevent them from opening the conversation. Employers also understand that employees work to meet their financial needs. While employers may face budget constraints or other considerations in salary allocation, strong management also recognizes the importance of nurturing growth among employees, both in compensation and job responsibilities.

Nonetheless, employees should focus the discussion on broader economic conditions like inflation, not on their personal budget items. By acknowledging the economic environment outside of the employer’s control, employees can then respectfully request their salary be adjusted for inflation.

Employees with a record of strong results can also gather data or performance reviews to demonstrate their contributions to the team beyond the expectations of their role. In doing so, employees can frame a salary increase as a celebratory recognition of the mutually successful partnership between employee and employer and an investment in the relationship.

Be flexible if negotiations stall

If employers decline to adjust an employee’s salary for inflation, employees should not give up on negotiating additional compensation or benefits. Rather than a pay raise, employees can ask for reimbursement for gas mileage or additional remote days to cut down on their commutes. If management declines a pay raise based on timing, employees can acknowledge that management may face budgetary constraints, remaining flexible but firm. For instance, a compromise may involve revisiting the discussion in three to six months.

As employees face record-breaking inflation, it remains critical to consider the risks of departing one role for another. By implementing best practices in salary negotiations, employees can secure a salary increase that matches inflation, avoid the uncertainty of job-hopping and invest in the future at their current company.

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Jill Chapman is a senior performance consultant with Insperity,a leading provider of human resources and business performance solutions.

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