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This paper proposes a novel framework for the cross-layer design and optimization of wireless networks based on the use of discrete time Markov chains (DTMC) jointly modeling the PHY layer and MAC sublayer. The QoS performance at the DLC layer is included through a multidimensional DTMC jointly describing the statistical behavior of the arrival process, the queuing system and the PHY/MAC layers. A cross-layer design based on the DTMC analytical model is proposed. This cross-layer scheme aims at maximizing the average throughput of the system with constraints on the maximum tolerable average packet loss and delay.