* Frankfurt shares close down 6.4 percent
* Jobs survived pancreatic cancer in 2004
* Underwent liver transplant two years ago
* Jobs will continue to be involved in strategic decisions
* COO Tim Cook to take responsibility (Adds background)
By Gabriel Madway and Georgina Prodhan
SAN FRANCISCO/LONDON, Jan 17 (Reuters) - Apple Inc Chief Executive Steve Jobs is taking medical leave for the third time since 2004, sending its shares tumbling more than 8 percent as the surprise revived concerns over the long-term future of the iPhone- and iPad-maker.
The company disclosed the news early on a U.S. holiday when U.S. markets were closed and did not specify why or for how long its visionary leader would be absent. Jobs' latest leave comes nearly two years to the date after he took a six-month break to undergo a liver transplant.
"At my request, the board of directors has granted me a medical leave of absence so I can focus on my health," Jobs, 55, wrote in an email to staff published on a regulatory newswire. "I love Apple so much and hope to be back as soon as I can."
Unlike the previous announcement, Apple did not say when Jobs would return, driving up the worst fears about Jobs' medical condition. An Apple spokesman declined to comment further.
"This time around you have to question his ability to bounce back," said Hudson Square Research analyst Daniel Ernst.
Jobs, a survivor of pancreatic cancer, said Chief Operating Officer Tim Cook would take responsibility for day-to-day operations once again, but he would remain as CEO and be involved in major strategic decisions.
Apple shares closed 6.2 percent lower in Frankfurt. Nasdaq futures fell 1.29 percent.
In recent days, Apples shares reached new all-time highs after announcing its iPhone would be available to customers of Verizon Wireless, the largest U.S. mobile operator.
JOBS KEY TO APPLE REBIRTH
Apple's destiny has been closely tied to Jobs, the short-tempered and charismatic leader who rescued the computer maker from near death in 1996 after a 12-year absence from the company he co-founded.
The launch of the iPhone, a smartphone with a touchscreen in 2007, and the iPad, a tablet computer in 2010, forged new business lines for the company that created the personal computing category and helped lead the technology industry into new directions.
Analysts said the effect on Apple's operations should be limited in the short term, since its product line-up was strong.
The next version of the iPad, the iPad 2, is still expected to be announced in the coming weeks. The splashy debut of a digital newspaper with News Corp, though delayed by a technical glitch, is also on track to be launched shortly.
Jobs' absence would be a bigger concern if it became prolonged. Cook ran day-to-day operations during Jobs' last absence in 2009.
"This will come as a surprise to Apple investors and definitely take some shine off the Apple stock," said Alexander Peterc, an equity analyst at Exane.
"But even if Steve Jobs never returns to Apple, I would not expect a visible, tangible impact on how Apple is executing over the next couple of years."
Although Apple has not articulated a clear succession strategy, Cook, whose name routinely appears on the short list for top jobs at other technology firms, is widely seen as the heir apparent.
Between the announcement of Jobs' 2009 medical leave until his return, Apple shares rose 60 percent under Cook's watch.
Still, it is far from certain whether Cook has the strategic vision that Jobs so famously possesses.
Cook was named chief operating officer in 2005 and is seen as a master of Apple's complex and far-flung supply chain. He also manages sales, service and support and leads the company's Mac computer division, where sales have been surging over the past few years.
Cook took over day-to-day operations in 2009 when Jobs took leave to have a liver transplant. He also steered the company in 2005, after Jobs had surgery for pancreatic cancer.
APPLE'S FUTURE
Gleacher & Co analyst Brian Marshall said investors would undoubtedly question Apple's long-term momentum, given Jobs' outsized role in developing the company's hit products.
"Clearly Steve is a visionary. And at $350 a share this is going to weigh on investors," he said.
Richard Windsor, global technology specialist at Nomura, agreed that Jobs' absence should not have a fundamental effect, but added: "Perception of the company is another matter."
"Steve Jobs is seen by the market to be a major force in Apple's strategic direction. If his pancreatic cancer has returned, one could be quite worried."
Apple has been notoriously close-mouthed about Jobs' medical condition. He had surgery in 2004 for an unusual type of tumor on his pancreas called a neuroendocrine tumor -- which often is not quite as deadly as pancreatic cancer. The tumors can cause hormone imbalances, like the one that prompted Jobs to take medical leave in 2009.
Jobs had a liver transplant in 2009, and organ transplant recipients sometimes have recurring health issues for life, in part because they often must take immune-suppressing drugs to prevent organ rejection.
Jobs was noticeably thin following his transplant surgery in 2009, and he still appeared so at recent Apple events, something that did not go unnoticed.
But the CEO said last summer he was feeling "great," in response to a question from a reporter.
Apple is due to report quarterly results on Tuesday, and is expected to say that revenues rose 50 percent as sales of its iPad tablet computer grew on momentum of the popular iPhone and earlier iPod. (Reporting by Gabriel Madway in San Francisco, Georgina Prodhan in London, Maggie Fox in Washington D.C., and Sweta Singh in Bangalore; Editing by Savio D'Souza, Martin Golan and Richard Chang)