Mixed lineage leukemia (MLL/KMT2A) rearrangements (MLL-r) are one of the most frequent chromosomal aberrations in acute myeloid leukemia. We evaluated the function of Meningioma 1 (MN1), a co-factor of HOXA9 and MEIS1, in human and murine MLL-rearranged leukemia by CRISPR-Cas9 mediated deletion of MN1. MN1 was required for in vivo leukemogenicity of MLL positive murine and human leukemia cells. Loss of MN1 inhibited cell cycle and proliferation, promoted apoptosis and induced differentiation of MLL-rearranged cells. Expression analysis and chromatin immunoprecipitation with sequencing from previously reported data sets demonstrated that MN1 primarily maintains active transcription of HOXA9 and HOXA10, which are critical downstream genes of MLL, and their target genes like BCL2, MCL1 and Survivin. Treatment of MLL-rearranged primary leukemia cells with anti-MN1 siRNA significantly reduced their clonogenic potential in contrast to normal CD34⁺ hematopoietic progenitor cells, suggesting a therapeutic window for MN1 targeting. In summary, our findings demonstrate that MN1 plays an essential role in MLL fusion leukemias and serve as a therapeutic target in MLL-rearranged acute myeloid leukemia.

In this study, the plasmid content of clinical and commensal strains was analyzed and compared. The replicon profile was similar in both populations, except for L, M, A/C, and N (detected only in clinical strains) and HI1 (only in commensal strains). Although I1 and F were the most frequent replicons, only IncI1, sequence type 12 (ST12) was associated with bla_CMY-2 in both populations. In contrast, the widespread resistant IncF plasmids were not linked to a single epidemic plasmid.

As home sellers commonly propose to state a lower price in the sale contract than the actual transaction value, home buyers have to bear additional risks from such real estate transactions.

The remains of three slaves found in Mexico contain the earliest signs of the hepatitis B virus and yaws bacteria in the Americas, suggesting transatlantic slavery introduced these diseases

The NCAA struck back at the University of Kansas and its men's basketball program Thursday, calling five Level I violations that are alleged to have occurred “egregious” and arguing that they undermine and threaten" college athletics.

Follow our live coronavirus updates HERE Coronavirus: The symptoms

The CNN anchor has gone viral after putting a positive spin on the news

A goose has taken advantage of the coronavirus lockdown to nest in one of the north of England's busiest transport hubs.

Elderly residents of a Staffordshire street woke up this morning to find their gardens had been ransacked by vandals.

POLICE have praised the jail terms handed to two men who launched a drink and drug-fuelled ‘campaign of terror’ across west Oxfordshire.

As lightning crackled in the clouds, the GOES-16 weather satellite watched all the violent action from 22,000 miles away.

From love triangles to the bond between mothers and daughters, performers step into the relationships minefield

• Hottest front-room seats: the best theatre and dance online

The beady-eyed character of Iseult Golden’s monologue could be an Alan Bennett creation: steely and unsentimental, she speaks her mind smartingly in a video message to her daughter who refuses to talk to her. Her tone is spiky at first but Marion O’Dwyer’s wry, understated delivery gives the drama a quietly pained depth. Part of the Abbey theatre’s monumental series Dear Ireland, it captures the bristling complexities of love between mothers and daughters in eight bittersweet minutes.

Presenter deemed president the 'moron-in-chief'

The actress has resurfaced as a TikTok star

It's the first European airline to make face masks mandatory for passengers

The 'Underworld' actress finds it frustrating that people consider women to be "risqué" for doing things like dating or getting tattoos

EXCLUSIVE

The Workers Compensation Commission finds in favour of a former House Rules contestant who claimed she was now unemployable because of the negative way she was portrayed on the Channel Seven show.

A court hears an Australian Federal Police officer told ABC lawyers he did not want to see "sensationalist headlines" prior to a raid of the broadcaster's Sydney headquarters this year.

The first report from the 10-month royal commission into aged-care standards offers blunt condemnation of the system, describing it as "unkind and uncaring" and fails to deliver safe care.

Man Utd defender Timothy Fosu-Mensah has been asked to name the best XI of players he has played with during his career.

Here's a look at the number of coronavirus cases in Kansas and the latest news about the COVID-19 outbreak.

La tragédie dans les CHSLD conduit forcément à chercher des responsables.

The feature directing debut for actor Clark Duke, "Arkansas" amiably places Liam Hemsworth in a dangerous world of low-level criminals.

PTC Therapeutics has reached an agreement to acquire Censa Pharmaceuticals and its lead asset, an experimental metabolic disorder therapy that is now being prepared for a pivotal study. The deal, announced after the market close Wednesday, will bring South Plainfield, NJ-based PTC (NASDAQ: PTCT) another compound for its pipeline of rare disease drugs. Wellesley, MA-based […]

In another strategic M&A deal announced so far this month, PTC Therapeutics has entered into an agreement…

The Department today announced a settlement that, if approved by the court, will resolve allegations in a lawsuit the Department filed on behalf of Randall A. Slocum, an Air Force Reservist, against the city of Iola, Kan. The complaint, filed in December 2008, alleged that the city of Iola violated the Uniformed Services Employment and Reemployment Rights Act of 1994 (USERRA) by taking into consideration Slocum’s military service obligations when it disciplined him and denied him a wage increase.

Two petroleum refiners have agreed in separate settlements to spend a total of more than $141 million in new air pollution controls at three refineries in Kansas and Wyoming.

The Department issued a statement today after JBS and National Beef announced the abandonment of the JBS/National Beef transaction, which the Department had filed suit to block in October.

Joseph P. Galichia, M.D. and Galichia Medical Group P.A., a Kansas cardiologist and his practice group, have agreed to pay the United States $1.3 million to settle claims that the physician and his group violated the False Claims Act between 2001 and 2006, by submitting false claims to Medicare.

Lazare Kabaya Kobagaya, 82, of Topeka, Kan., was arrested today on charges of naturalization fraud and misuse of an alien registration card. According to the indictment, Kobagaya allegedly participated in genocidal activities during the 1994 Rwandan conflict including mobilizing attackers to commit arson and murder. Kobagaya is alleged to have failed to disclose his alleged participation in these activities during his immigration and naturalization processes.

A federal grand jury in Fort Smith, Ark., has indicted five men from the Donaldson, Ark., area on federal civil rights charges as well as charges of making false statements to the FBI.

The Department has filed a complaint in U.S. District Court in Arkansas against the City of Marion alleging it subjected Stacy D. Allen, an African-American and a former City part-time patrol officer, to discrimination on the basis of his race when he was not selected for either of two full-time patrol officer positions in the Marion Police Department.

A Kansas woman pleaded guilty to making a false statement to the FBI during an investigation into allegations of fraud against the Federal Communications Commission’s (FCC) E-Rate program. According to the plea agreement, filed today in U.S. District Court in Kansas City, Kan., Mary Jo LaDuron, aka Mary Jo Gault, of Leavenworth, Kan., lied to FBI agents who were investigating allegations of fraud against the E-Rate program.

Dustin I. Nix, 21, of Donaldson, Ark., pleaded guilty today in federal court in Hot Springs, Ark., to two federal civil rights charges for his role in a conspiracy to force a woman and her young children from their home in Donaldson because she associated with African Americans.

Everett Cooney waived indictment and pleaded guilty in court in Little Rock, Ark., to a federal charge of sex trafficking an underage female. Chief U.S. District Judge J. Leon Holmes accepted Cooney’s guilty plea.

A pipeline company and two of its former operating firms will jointly pay a civil penalty of $3.65 million to resolve violations of the Clean Water Act resulting from anhydrous ammonia spills in Nebraska and Kansas, the Justice Department and U.S. Environmental Protection Agency announced today. The spills which occurred in 2004 resulted in significant fish kills in surrounding waterways.

Jacob A. Wingo, Richard W. Robbins, Clayton D. Morrison and Darren E. McKim pleaded guilty today and yesterday to conspiring to drive a woman and her children from their home in Donaldson, Ark., because they associated with African Americans. A fifth defendant, Dustin Nix, 21, pleaded guilty to similar charges in July 2009.

The United States has asked a federal court in Kansas City, Kan., to bar Carlos Cruz, aka Carlos Ruano-Cruz, from preparing tax returns for others.

The department has reached a settlement with the city of Marion, Ark., that, if approved by the U.S. District Court for the Eastern District of Arkansas, will resolve the department’s lawsuit against the city alleging race discrimination in employment in violation of Title VII of the Civil Rights Act of 1964, as amended.

Dustin Nix of Donaldson, Ark, was sentenced today in federal court in Fort Smith, Ark, on federal civil rights charges related to a conspiracy to drive a woman and her children from their home because they associated with African-Americans.

After conducting a careful investigation of the proposed transaction between Oracle and Sun, the Department’s Antitrust Division concluded that the merger is unlikely to be anticompetitive.

A federal court in Kansas City, Kan., has permanently barred Carlos Cruz, also known as Carlos Ruano-Cruz, from preparing tax returns for others.

Jacob Wingo, Clayton Morrison, Darren McKim and Richard Robins were sentenced today and yesterday in federal court in Hot Springs, Ark., on federal civil rights and obstruction of justice charges related to a conspiracy to drive a woman and her children from their home in Donaldson, Ark., because the victims associated with African-Americans.

Leonard Douglas “Doug” LaDuron also was ordered to pay $238,607 in restitution.

Paul Schlesselman pleaded guilty to one count of conspiracy, one count of threatening to kill and inflict bodily harm upon a presidential candidate, and one count of possessing a firearm in furtherance of a crime of violence.

General Re has admitted that its most senior management engaged in a scheme to falsely inflate AIG’s reported loss reserves, a key indicator of financial health to insurance industry analysts and investors.