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Najib, reading out a statement at a news conference, said Malaysia had not been able to verify what caused the Boeing 777-200 to crash while on a flight from Amsterdam to the Malaysian capital, Kuala Lumpur, but it had not made a distress call.
But he said he had agreed in talks with US President Barack Obama that investigators must get full access to the site of the crash.
"The Ukrainian authorities believe that the plane was shot down," Najib said in the statement. "At this stage, however, Malaysia is unable to verify the cause of this tragedy. But we must, and we will, find out precisely what happened to this flight. No stone will be left unturned."
"If it transpires that the plane was indeed shot down, we insist that the perpetrators must swiftly be brought to justice."
Ukraine accused "terrorists" - militants fighting to unite eastern Ukraine with Russia - of shooting down the plane. The rebels denied responsibility.
US Vice President Joe Biden said the downing of the airliner was apparently was "not an accident" and that it was "blown out of the sky".
Najib said also that Malaysia was sending a special flight to Kiev with a disaster assistance and rescue team.
"An international team must have full access to the crash site and no one should interfere with the area, or move any debris, including the black box," he said.
Malaysia Airlines said earlier air traffic controllers lost contact with Flight MH-17 as it flew over eastern Ukraine toward the Russian border with 280 passengers and 15 crew aboard. Flight tracking data indicated it was at its cruising altitude of 10,000 metres when it disappeared.
That would be beyond the range of smaller rockets used by the rebels to bring down helicopters and other low-flying Ukrainian military aircraft - but not of Soviet-era SA-11 ground-to-air missiles which a Ukrainian official accused Russia of supplying to the rebels.
The loss of MH-17 is the second disaster for Malaysia Airlines this year, following the mysterious loss of Flight MH-370. It disappeared in March with 239 passengers and crew on board on its way from Kuala Lumpur to Beijing.
"This is a tragic day, in what has already been a tragic year, for Malaysia," Najib said.
Relatives of passengers aboard the airliner gathered at the Kuala Lumpur airport early on Friday, demanding information, in particular confirmation of those on board.
"We need to know the list. The list. That is all," one man told reporters, referring the flight's passenger list.